This weeks case focussed on the importance frailty assessment in making treatment decisions for an elderly patient with Diffuse large B cell lymphoma. This is an important topic as DLBCL affects an older population with mean age at diagnosis of 67 years. Historically there have been poor outcomes in the older frailer cohort of lymphoma patients. There is significant under representation in clinical trials and difficulties in evaluating fitness have hindered progress in improving outcomes. The role of the multi-disciplinary team and careful assessment of fitness is key to ensure patients are treated in an appropriate patient centred manner.
There is increasingly a recognition of the importance of focussing on cancer in an elderly population. Cancer is a disease that predominantly affects the elderly with cancer incidence peaking at 80-85 years of age in the UK. In the UK older patients are less likely to be referred via 2WR pathways and yet are more likely to have cancer compared to other age groups. Patients over 75 years account for a third of diagnoses of cancer in UK but according to recent Macmillan data account for over half of the total deaths in the UK.
The guiding principles in an older population with cancer should be according to a recent BJGP article adding “quality to years and not always years to life”.
There are often limitations to intensity of therapy that can be delivered and open and honest shared decisions are needed here
Objective measures of frailty are essential to underpin and frame the conversations that help in shared decision making.
A recent BJHaem article by cordoba et al on frailty assessment advocates frailty assessments roles in shared decision making. Goode et al in their review on frailty in the older patient point out that frailty and haematological malignancy are bi-directional in their relationship both having an impact on each other and this interplay influences overall outcomes. They give many examples in their excellent review such as cancer related anaemia leading to deterioration in cardiac function and renal function leading to worsened anaemia. Infection post chemotherapy and mild cognitive impairment leading to delirium then a fall and hip fracture with worsening of delirium and anaemia. These situations are all too commonly seen in everyday clinical practice and often these adverse outcomes could have been predicted if more time had been given upfront into careful assessment of the patient in front of the clinician. .
When shared decision making is needed when faced with an elderly patient with haematological malignancy we need to consider ways of evaluating frailty, co-morbidity functional status and ADLs.
Frailty is defined as an age-related state of increased vulnerability and poor resilience to acute stressors. This can be assessed using a variety of frailty assessments:
G8 Screen – short test to indicate when a more detailed assessment is indicated if score <15 points. There is some limited data that show correlation between low G8 score and mortality in DLBCL.
Vulnerable elders survey, Groningen frailty indicator and Flemish version of triage risk score – some limited data exploring their use in showing inferior outcomes in NHL.
These tools are not perfect but help as short screening tools and will help highlight issues that you may not have immediately picked out when you take the usual social history.
Co-morbidity is also an important consideration when contemplating treating an older patient with a haematological malignancy.
Charlton Co-morbidity index – This is a helpful screening tool that can help evaluate a 1 year and 10 year mortality for the individual in clinic without their haematological malignancy and this can be helpful to add context to frame difficult decisions. This index is used alongside age, ADL, Instrumental ADL in myeloma patients to evaluate patients into fit, intermediate fit and frail groups for therapy by the International myeloma working group.
Cumulative illness rating scale – validated tool for contemplating co-morbidity based on 14 items. This has been used by the Italian Lymphoma foundation alongside Age >80 years, ADL, and Instrumental ADL to define “ fit, unfit and frail” elderly patients with DLBCL and has been shown to be effective in highlighting the frail patients who have same outcomes if treated for cure vs palliative approach. Outcomes for the three groups were 3 year OS of 87%, 69% and 42% and this was the first score system that has been shown to stratify patients outcomes by integrating clinical and geriatric assessment in lymphoma patients.
ACTIVITIES OF DAILY LIVING:
ADL – 6 item scale to assess function. Integral to INMWG and also Italian lymphoma foundation work on frailty.
Instrumental ADL – 8 item questions to assess functionality.this is also part of INMWG and Italian foundation work on frailty.
The outcomes of considering the above should be to prompt consideration of any methods that could help mitigate overall frailty. These steps are simple but may have tangible benefits for patients. Examples include:
Consider polypharmacy and interactions.
Dietician review for nutrition optimisation.
Considering bone protection if using steroids to prevent fractures.
Occupational therapy for ADL issues.
Physiotherapy to enhance fitness.
Social service referral to improve support or provide pendant alarm in case of falls etc
CRASH chemotherapy risk assessment scale for high age patients – 15% validation cohort had lymphoma.
CARG cancer and ageing research group – help to evaluate toxicity of therapy not validated in lymphoma population.
OTHER DLBCL SPECIFIC CONSIDERATIONS
In our case a steroid pre-phase was used and this can be very helpful in evaluating fitness in a new lymphoma patient where frailty is felt to be mainly due to disease.
Gode et al highlight the importance of consideration of what is causing the frailty is it the haematological malignancy or general frailty and this can be a real barrier to effective decision making around treatment when a patient isn’t known before and a trial of steroids can be very helpful here
1mg/kg Prednisolone for 5-7 days has been shown indirectly to reduce treatment related mortality in high grade lymphoma. This data is from LYSA study where there were 12 deaths in RHOP and R mini CHOP arms and none in the O CHOP arm where steroid pre phase was used as standard.
R mini CHOP has been shown to be effective in an older patient cohort and is the standard therapy used for >80 years old patients. It has a 2 year OS of 59% and the survival curves do plateau indicating a durable response. It is important to state that in patients over 80 years the intended dose intensity is likely more important than the overall dose of anthracyclines used and there is very limited data to show any improved outcomes when using R CHOP at full dose compared to reduced doses for patients >80 years.
R CEOP is a valid option for management of elderly patients with impaired ventricular function and outcomes were comparable to R CHOP 58% vs 67% disease specific survival at 10 years.
Bone protection is an important issue post therapy with DLBCL with 11.4% risk of fracture in the first 18 months post RCHOP. This is an issue that can cause considerable co-morbidity and can be prevented if considered at start of therapy.
Postural drop and poor tolerance to steroid withdrawal are also common issues and a careful steroid wean and review of hypertension medications can also help deal with these issues.
Hopefully this case has provided you something to contemplate in your own experience of managing older patients with malignancy and there is an excellent review I have highlighted in the references if you wish to read more on this topic.
Excellent 4 part series of papers on haematological malignancy in older people available for free at :
(Includes Cordoba et al A comprehensive approach to therapy of haematological malignancies in older patients. Gode et al frailty assessment in the care of older patients with haematological malignancies)
Cordoba R, Luminaries S and Eyre T. The use of ffrailty assessments in treating older adults with aggressive lymphomas. BJHaem (2021) 194, 677-685.
Booth et al. Fractures are common within 18 months following first line RCHOP in older patients with diffuse large B cell lymphoma. Blood (2020). 4 (18): 4337-4346
Jones et al. Investigating cancer symptoms in older people. What are the issues and where is the evidence? BJGP (2020). 70(696):321-322.
Older people living with cancer Designing the future health care workforce;