Episode 7 - Medical Oncology

Theme:
Medical Oncology.

Participants:

Professor Nicholas Wilcken, Sarah Rashid, Bratati Karmakar, Harry Hong, Dr Pramod Chandru, Shreyas Iyer, Caroline Tyers, and Kit Rowe.

Discussion 1:
Thomas, B., Lo, W., Nangati, Z., & Barclay, G. (2021). Dexmedetomidine for hyperactive delirium at the end of life: An open-label single-arm pilot study with dose escalation in adult patients admitted to an inpatient palliative care unit. Palliative Medicine, 35(4), 729-737. https://doi.org/10.1177/0269216321994440.

Presenter - Sarah Rashid, physician trainee at Westmead Hospital.

Summary:

• Terminal agitation and delirium are difficult to define and even harder to design studies around which to improve its management.
• The current treatment algorithm advises the use of neuroleptics, benzodiazepines, opiates, and barbiturates; often at the cost of wakefulness and interaction with loved ones.
• Dexmedetomidine can provide rousable sedation, a decreased severity of delirium, analgesia, a decrease in secretions, and potential anti-emetic effects.
• The aim of this study was to describe a potential reduction in delirium and the presence of rousable sedation with dexmedetomidine in palliative care patients suffering terminal delirium, with a secondary aim to determine whether reduced opiate requirements were observed.
• There was a reduction in delirium (as measured by MDAS scores).
• Almost 50% of patients crossed over to routine care, with 27% of these due to family request for deeper sedation.
• 15 of the 22 patients required an increase in opiate dosing, however, there were no negative survival benefits and there was a notable reduction in the use of other PRN medications (such as, for secretions).
• Ultimately, this pilot demonstrated promise for the use of dexmedetomidine in these patients (and prompts the need for further research in this area).

Take-Home Points:

• There is minimal evidence even behind our standard of care for these patients (midazolam, neuroleptics, and barbiturates).
• This paper encourages us to think laterally about what medications can be used for these patients.
• Terminal delirium is distressing for patients and their families, and at present, our treatments provide comfort but at the expense of wakefulness and interaction.
• More research needs to be done into agents such as dexmedetomidine which could allow for a better-sedated experience.
• More research also needs to be done into the experience of the dying process for patients and their families.
• Families have large effects on the management of dying patients, and thus there is limited value in doing a study without measuring outcomes for both the patients and their families.

Discussion 2:
Wang, D., Salem, J., Cohen, J., Chandra, S., Menzer, C., & Ye, F. et al. (2018). Fatal Toxic Effects Associated With Immune Checkpoint Inhibitors. JAMA Oncology, 4(12), 1721. https://doi.org/10.1001/jamaoncol.2018.3923.

Presenter - Harry Hong - ED senior resident medical officer, at Westmead Hospital.

Summary:

• This study looks at immune checkpoint inhibitors targeting cytotoxic T lymphocyte antigen-4 (CTLA-4) and programmed death-1/ligand-1 (PD-1/PD-L1).
• There is increasing use of these agents individually and in combination for various cancers.
• This paper looks at multiple databases and analyzed data to characterize the rare but fatal side effects of these drugs.
• 613 fatal adverse effects were described: 193 associated with ipilimumab (anti-CTLA-4), 333 with anti-PD-1/PD-L1, and 87 in combination therapy (most commonly for the treatment of melanoma and lung cancer).
• The type of fatal adverse events differed between the treatment groups; with ipilimumab monotherapy associated mostly with colitis (70% of adverse events) compared with anti-PD-1/PD-L1 monotherapy where adverse events were more varied (colitis, pneumonitis, hepatitis) and combination regimens where there were additionally increased rates of myocarditis and myositis.
• The highest fatality rates were seen in myocarditis.
• The multicentre analysis also revealed the median time to onset of disease following commencement on therapy was 40 days with monotherapy and 14.5 days for those on combination treatment.
• Interestingly, the median time to steroid use for these patients was 5 days (suggested to be due to difficulty recognizing the diagnosis in these patients).

Take-Home Points:

• These drugs for some cancers have completely revolutionized treatment (they are not going away!).
• It is important to remember that the rate of fatal adverse events with these agents is still very low (particularly when compared with other oncology treatments).
• This data gives us information for what to be vigilant for when caring for these patients (particularly those presenting with non-specific symptoms and recent commencement on these agents).
• Take colitis seriously; it can be fatal.
• We are all learning; this is a new class of drugs with completely different toxicity to what we are used to – if in doubt ask the medical oncologist!

Discussion 3:
Biganzoli, L., Mislang, A., Di Donato, S., Becheri, D., Biagioni, C., & Vitale, S. et al. (2017). Screening for Frailty in Older Patients With Early-Stage Solid Tumors: A Prospective Longitudinal Evaluation of Three Different Geriatric Tools. The Journals Of Gerontology: Series A, 72(7), 922-928. https://doi.org/10.1093/gerona/glw234.

Presenter - Bratati Karmakar, physician trainee at Napean Hospital.

Summary:

• Frailty is a concept or syndrome which lacks a unified definition.
• It is broadly defined as a vulnerability to stressors such as illness or treatment, which may aid in patient prognostication.
• Currently, there is no single standardized frailty assessment tool to guide our clinical practice.
• The presence of frailty has been associated with increased mortality, increased frequency of hospitalizations, intolerance to treatments, and a reduction in quality of life.
• Data suggests that we as clinicians at the bedside are not accurate assessors of patient frailty.
• This study compares well-established (however cumbersome) frailty scores; the Balducci frailty criteria and the Fried frailty criteria, with the Vulnerable Elders Survey (VES-13) which may be easier to use and apply in the emergency setting (requiring only self-reported data from the patient).
• The outcomes measured were functional decline (or loss of an ADL) and mortality.
• 17% of patients were classified as frail using the Fried frailty criteria, and 25% when looking at the Balducci criteria and the VES-13.
• The Fried frailty criteria and the VES-13 both showed that the probability of a functional event was higher in the frail group (with time to functional decline being 13 months in the frail and 36 months in the non-frail group using the VES-13).
• Regarding mortality, all 3 tools demonstrated prognostic value for overall survival.
• Thus, according to this study, the VES-13 can be used to predict mortality and functional decline.
• However, there was poor concordance between the three tools, suggesting that no single ...