In this issue of ONCOLOGY,Winell and Roth review the veryimportant topic of assessment andtreatment of psychiatric symptoms inelderly cancer patients. Their reviewis comprehensive and practical. Thiscommentary further develops a numberof themes raised in their article.
In this issue of ONCOLOGY, Winell and Roth review the very important topic of assessment and treatment of psychiatric symptoms in elderly cancer patients. Their review is comprehensive and practical. This commentary further develops a number of themes raised in their article. The authors note that psychiatric symptoms are common in both geriatric patients and the general population of cancer patients. Much attention has been paid recently to the challenging issue of diagnosis and treatment of psychiatric symptoms among patients with complex medical problems including cancer.[1-3] Psychiatric symptom control affects patient comfort, quality of life, and possibly even immune system function.[4,5] Despite this increased attention, many cancer patients still receive inadequate treatment for psychiatric symptoms.[1] Although nearly half of cancer patients develop significant symptoms of depression during their illness, there is still no consensus about proper screening and case identification methods.[1] Detection of psychiatric symptoms and cognitive impairment in the primary care setting is incomplete.[6,7] To reverse this, oncologists and primary care physicians must view diagnosis and treatment of psychiatric symptoms as a central component of their efforts with cancer patients. Depression
The authors note that depressed mood is a symptom warranting further investigation and consideration of a differential diagnosis. Major depression is a syndrome, comprising numerous symptoms including sad mood, that must be distinguished from other clinical entities such as adjustment disorder or major depression caused by general medical conditions. The importance of depression identification and treatment in cancer patients was recently highlighted by a National Institutes of Health State-ofthe- Science Conference.[1] The differential diagnosis of the sad cancer patient needs to extend beyond these diagnoses alone. Demoralization is a well-defined clinical entity despite not being included in the Diagnostic and Statistical Manual of Mental Disorders.[8,9] Demoralization is very common in medically ill patients and can be differentiated from major depression.[10] The clinical entity of demoralization was first conceptualized by Dr. Jerome Frank and identified as the emotional state common to individuals who responded well to psychotherapy.[11] It can be thought of as a normal response to very difficult life circumstances in which the person "is no longer able to bear up under adversity," leading to sadness, apprehension, pessimism, uncooperativeness, and other signs of emotional distress.[12] In contrast, the term adjustment disorder implies that the patient's reaction is pathologic in nature; demoralization emphasizes the normality and comprehensibility of the reaction in light of the patient's life circumstances.[12] This distinction is critical in treatment plan formulation. Demoralization is best understood in relationship to the meaning of the difficult life circumstances; efforts to combat demoralization must be organized around these meaningful themes. These themes may include fear of pain or death, disappointment over unmet goals, financial pressures, and worry about the welfare of surviving family members. Combating demoralization through increasing physician support, marshalling necessary resources, or engagement in formal psychotherapy must effectively address these meaningful themes.[13,14] The differential diagnosis of sad mood in the cancer patient must also include delirium, a syndrome that cancer patients are at significant risk of developing. The delirious patient can primarily appear sad, distracting attention from the underlying but hierarchically more important cognitive impairment.[15] One final point regarding depression in cancer patients is its relationship to pain. The authors correctly point out that pain is an important cause of depression and anxiety. However, it is important to note that inadequately treated depression may significantly amplify the experience of pain and that treatment of depression may lead to an improvement in pain. Delirium
The authors note that delirium is common in elderly medical patients, is associated with increased mortality, and is often multifactorial in etiology. A number of additional points will be added to complement their discussion. Diagnosis of delirium is challenging for a number of reasons. First, because delirium is often associated with symptoms such as depressed or anxious mood, behavioral disturbance, hallucinations, delusions, and sleep disturbances, the initial diagnosis may focus on the psychiatric disturbance and miss the underlying delirium. Second, the cognitive disturbance in delirium can be subtle, and in the medically ill elderly patient may be passed off as "normal." Finally, certain clinical features (discussed below) of the course of delirium may make it difficult to diagnose in a brief single examination. The hallmark of delirium is an altered level of alertness and ability to attend to the environment. Usually these functions are diminished; in certain conditions, such as delirium tremens (from alcohol, benzodiazepine, or barbiturate withdrawal), these functions are increased. Neuropsychiatric symptoms are highly prevalent in delirium, but are not necessary for the diagnosis of delirium. Important supportive clinical features include a waxing- waning pattern of impairment and sleep-wake disturbance. Therefore, diagnosis of delirium is facilitated by performing serial examinations, reviewing others' examinations performed throughout the day (eg, inpatient nursing notes), and obtaining detailed historical information from knowledgeable informants about the course of the patient's cognitive changes. An electroencephalogram may be useful in demonstrating a pattern of diffuse slowing of electrical activity, particularly if there is a baseline study with which to compare.[16] In patients with known dementia, establishment of the patient's cognitive baseline through record review or informant interview allows for a comparison with the current mental status.[17] The authors enumerate several etiologies for delirium; there are additional important ones for the elderly cancer patient that should be considered when evaluating delirium. Infections, particularly otherwise asymptomatic urinary tract infections, are important causes of delirium and should be particularly considered in immunocompromised patients. In addition to the medications enumerated, benzodiazepines, commonly used to treat anxiety in cancer patients, can cause delirium; many antibiotics can cause delirium as well. Other common offenders include anticholinergic medications, antihistamines, and commonly used psychotropic medications including antidepressants and antipsychotics.[ 16] Consideration should be given to implementing delirium-prevention measures, particularly in hospitalized elderly patients. A number of welldesigned prospective controlled trials have demonstrated efficacy in reducing the incidence of delirium in this population.[18,19] Neuroleptic use in the delirious patient should be limited to treatment of clinically disturbing hallucinations, delusions, or agitation, and should not be considered a treatment of delirium per se. In the elderly patient, doses should be minimized. Ultimate treatment of the delirium occurs when the etiology is discovered and reversed. In the interim, careful attention to patient safety is imperative. Specialist Referral
Despite careful attention to psychiatric symptomatology by the primary care physician or oncologist,some symptoms may prove refractory to treatment. This should prompt referral to a geriatric psychiatrist for further evaluation and management. This referral may facilitate the implementation of more intense or sophisticated psychotherapy and pharmacotherapy than can be provided by a nonspecialist.[20] Conclusion
Psychiatric symptoms present in elderly patients with cancer range from normal emotional reactions to the stresses associated with cancer and its treatment, to more dramatic symptoms requiring urgent investigation and intervention. Familiarity by the primary care physician and the oncologist with the natural history of common psychiatric conditions, the historical and mental status findings that differentiate these conditions, and certain basic approaches to treatment and referral will greatly facilitate the proper assessment and treatment of these conditions.
The authors have no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.
1. Patrick DL, Ferketich SL, Frame PS, et al: National Institutes of Health State-of-the- Science Conference Statement: Symptom management in cancer: Pain, depression, and fatigue, July 15-17, 2002. J Natl Cancer Inst Monogr (32):9-16, 2004.
2. Iosifescu DV, Bankier B, Fava M: Impact of medical comorbid disease on antidepressant treatment of major depressive disorder. Curr Psychiatry Rep 6:193-201, 2004.
3. Angelino AF, Treisman GJ: Major depression and demoralization in cancer patients: Diagnostic and treatment considerations. Support Care Cancer 9:344-349, 2001.
4. Lehto US, Ojanen M, Kellokumpu- Lehtinen P: Predictors of quality of life in newly diagnosed melanoma and breast cancer patients. Ann Oncol 16:805-816, 2005.
5. Zhou FL, Zhang WG, Wei YC, et al: Impact of comorbid anxiety and depression on quality of life and cellular immunity changes in patients with digestive tract cancers. World J Gastroenterol 11:2313-2318, 2005.
6. Banazak DA: Late-life depression in primary care. How well are we doing? J Gen Intern Med 11:163-167, 1996.
7. Boustani M, Peterson B, Hanson L, et al: Screening for dementia in primary care: A summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med 138:927- 937, 2003.
8. American Psychiatric Association, Task Force on DSM-IV: Diagnostic and Statistical Manual of Mental Disorders: DSM-IV, 4th ed. Washington, DC, American Psychiatric Association, 1994.
9. Clarke DM, Kissane DW: Demoralization: Its phenomenology and importance. Aust N Z J Psychiatry 36:733-742, 2002.
10. Mangelli L, Fava GA, Grandi S, et al: Assessing demoralization and depression in the setting of medical disease. J Clin Psychiatry 66:391-394, 2005.
11. Frank JD, Frank J: Persuasion and Healing: A Comparative Study of Psychotherapy, 3rd ed. Baltimore, Johns Hopkins University Press, 1991.
12. Slavney PR: Diagnosing demoralization in consultation psychiatry. Psychosomatics 40:325-329, 1999.
13. Kash KM, Mago R, Kunkel EJ: Psychosocial oncology: Supportive care for the cancer patient. Semin Oncol 32:211-218, 2005.
14. Frank JD. Psychotherapy: The restoration of morale. Am J Psychiatry 131:271-274, 1974.
15. Farrell KR, Ganzini L: Misdiagnosing delirium as depression in medically ill elderly patients. Arch Intern Med 155:2459-2464, 1995.
16. Slavney PR: Psychiatric Dimensions of Medical Practice: What Primary-Care Physicians Should Know About Delirium, Demoralization, Suicidal Thinking, and Competence to Refuse Medical Advice. Baltimore, Johns Hopkins University Press, 1998.
17. Fick DM, Agostini JV, Inouye SK: Delirium superimposed on dementia: A systematic review. J Am Geriatr Soc 50:1723-1732, 2002.
18. Inouye SK, Bogardus ST, Jr, Charpentier PA, et al: A multicomponent intervention to prevent delirium in hospitalized older patients. N Engl J Med 340:669-676, 1999.
19. Marcantonio ER, Flacker JM, Wright RJ, et al: Reducing delirium after hip fracture: A randomized trial. J Am Geriatr Soc 49:516-522, 2001.
20. Jones RD: Depression and anxiety in oncology: The oncologist’s perspective. J Clin Psychiatry 62(suppl 8):52-55, discussion 56-57, 2001.
Efficacy and Safety of Zolbetuximab in Gastric Cancer
Zolbetuximab’s targeted action, combined with manageable adverse effects, positions it as a promising therapy for advanced gastric cancer.
These data support less restrictive clinical trial eligibility criteria for those with metastatic NSCLC. This is especially true regarding both targeted therapy and immunotherapy treatment regimens.