Case-Based Clinical Approaches for Clinicians

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SPECIAL REPORT: PSYCHO-ONCOLOGY, PART II

To take care of cancer patients is an enormous privilege, but it also involves deploying everything in your toolbox: the emotional, the
psychological, the scientific, the epidemiologic.
– Siddhartha Mukherjee, The Emperor of All Maladies

Overcoming the stigma of both mental illness and cancer, psycho-oncology has emerged as a subspecialty within the fields of consultation-liaison psychiatry and oncology, rapidly evolving as a model of care (Figure 1). It has also become a robust area of research for cancer patients, families, caregivers, and clinicians. In the preface of the 3rd edition of the textbook Psycho-Oncology, Jimmie C. Holland, MD, a pioneer and major contributor to the field, wrote “the first opportunity to move the field forward occurred in the 1970s, when patients began to be given their cancer diagnoses and we could study their emotional responses to their illness.”

Founded in the late 1970s under Holland’s leadership, the Department of Psychiatry and Behavioral Sciences at Memorial Sloan-Kettering Cancer Center (MSKCC) in New York has served as a major mecca for clinical care and research in the field (William S. Breitbart, MD, a renowned clinician and researcher, currently serves as the department chair). The department’s foundation laid the groundwork for the establishment of accredited PGY-5 fellowship training programs in consultation-liaison psychiatry via the Academy of Consultation-Liaison Psychiatry (ACLP) with subspecialization in psycho-oncology, specifically at MSKCC, Dana-Farber Cancer Institute/Brigham and Women’s Hospital in Boston, and Princess Margaret Hospital in Toronto. Several ACLP fellowships now incorporate psycho-oncology didactics and clinical rotations into their training curriculum.

Evolving professional organizations include the American Psychosocial Oncology Society, International Psycho-oncology Society, and the psycho-oncology and palliative care special interest group of the ACLP. In 2007, the Institute of Medicine published Cancer Care for the Whole Patient: Meeting Psychosocial Health Needs, that addressed quality of life measures over the trajectory from diagnosis, treatment, survivorship, and end-of-life, which included psychological and existential distress (Figure 1).¹

Since the 1970s, cancer research and treatments have progressed exponentially, with rates of survival ever-increasing. Despite targeted therapies, cancer related neuropsychiatric sequalae prevailed—whether related to the specific cancer or treatment effects. This led to improved screening and interventions that include multimodal and interdisciplinary approaches and interventions as well psychological, psychopharmacological, integrative, nutritional, palliative, pain management, religious, and spiritual approaches (Figure 2). To that end, the following 2 cases illustrate prototypical approaches for 2 types of cancers: breast and central nervous system cancers. These are intended to be general overviews, with the caveat that many cancer patients are treated in non-urban settings where certain treatment modalities may not be available, and they will hopefully serve to guide treatment within the resources available locally.

Case 1

“Laura” is 38 years old, married with 2 young children. She has a history of depression and generalized anxiety disorder. She received a diagnosis of stage II multifocal ER+/HR+/HER2+ IDC breast cancer. She completed 8 of 12 planned cycles of neoadjuvant paclitaxel, trastuzumab, and palbociclib, which was discontinued due to neuropathies, fatigue, and depression. Although she had an excellent response, a left mastectomy and sentinel lymph node biopsy revealed more extensive disease. Laura was started on anti-estrogen therapy (tamoxifen), which was discontinued due to sudden mood changes, hot flashes, and myalgias. Before the diagnosis of breast cancer, her anxiety and depression had been well-controlled with fluoxetine.

Given her increased risk for recurrence of anxiety and depression, Laura was referred by her oncologist to psycho-oncology psychiatry because of her inability to tolerate tamoxifen, which is generally recommended for period of 5 to 15 years. Upon evaluation, Laura acknowledged anxiety and mood symptoms dating back to childhood, with a strong family history of anxiety and depression, and revealed she was a “perfectionist.” She was overwhelmed by both her diagnosis and treatment effects and worried about recurrence, concurrent with mood changes, hot flashes, body image, low libido, fatigue, poor concentration, passive suicidal ideation, and challenges working as an international recruiter for a Fortune 500 company.

Laura felt that she was a burden to her family. She was also overwrought with guilt and believed her work stress contributed to an immunosuppressed state resulting in her cancer diagnosis. Her husband, as her primary caregiver and caregiver for their 2 young children while working from home, was experiencing burnout. While raised as a Catholic, Laura had begun to question her faith, believing her diagnosis was a form of punishment from God.

Although her anxiety and depression were relatively well-controlled on fluoxetine prior to her cancer diagnosis, a switch from fluoxetine to a selective serotonin-norepinephrine reuptake inhibitors such as venlafaxine was recommended, given fluoxetine cytochrome P-450 (CYP) 2D6 strong inhibition in the conversion of tamoxifen (the pro-drug) to endoxifen (the active metabolite). By contrast, venlafaxine is a weak CYP2D6 inhibitor (Figure 3). With indications for anxiety and depression, venlafaxine is used off-label for hot flashes and neuropathies. Despite concerns about prescribing medications with marked CYP2D6 inhibition (eg, paroxetine, fluoxetine) for patients receiving tamoxifen for adjuvant treatment of breast cancer, recent studies are mixed regarding a relationship between CYP2D6 activity and cancer recurrence. Laura was given referrals to psychology, breast cancer support groups, palliative care (for pain and other symptom management), nutrition, chaplaincy services, and integrative medicine as well as caregiver support resources for her husband.

Over time, anxiety and depression were better controlled on venlafaxine, in addition to better targeting hot flashes, neuropathies, and myalgias, which allowed Laura to resume tamoxifen. What persisted were changes to her concentration, which she described as “mental clouding and fatigue,” often referred to as “chemo-brain,” from the effects of anti-estrogen therapy-induced menopause. Because some studies have shown benefits from psychostimulants (modafinil and armodafinil²), Laura was prescribed methylphenidate, which improved concentration and focus and allowed her to return to work. However, it is important to consider metastasis and CNS involvement on the differential when evaluating for any cognitive or behavioral status changes, with a low threshold for neuro-psychological testing, neurological workup, and imaging.

Laura was better able to accept the treatment-related changes to her body, the cancer diagnosis, and the fears of recurrence through acceptance and commitment therapy (ACT), and cognitive behavioral therapy (CBT) helped with sleep and fatigue. She derived excellent peer support in her breast cancer support group and was strongly encouraged to modify her work schedule by other members of the group.

Given emerging evidence supporting the influence of diet and exercise on the neuroendocrine and inflammatory pathways, a nutrition consult recommended a ketogenic diet as well as integrative approaches such as yoga, acupressure, and acupuncture. Chaplaincy was instrumental in helping her reframe and realign her religious beliefs and values, effectively assuaging underlying guilt related to her diagnosis. Her husband engaged in caregiver support groups and adopted a more balanced approach in his various caregiving and work roles, which resulted in increased support at home and with childcare. Ultimately, the couple was able to engage in couple’s therapy to improve interpersonal communication and renew their relationship after feeling displaced by the cancer diagnosis.

Case 2

“Jonathan” is 34 years old with no formal psychiatric history. He received a diagnosis of oligoastrocytoma of the right temporal lobe, which was incidentally found after a motor vehicle accident. He underwent a resection followed by radiation and 1 year of temozolomide chemotherapy.

Five years later, after presenting to the emergency room with new onset seizures, his tumor was found to have progressed. It was recommended to proceed with a re-resection of the primary tumor bed. However, given the proximity to critical brain structures, the second surgery required an awake surgery with brain mapping to avoid potentially devastating permanent impairments. Following the second surgery, the patient experienced delirium secondary to steroid-induced psychosis. The inpatient consultation-psychiatry service recommended minimizing steroids to the extent possible while starting olanzapine for sleep and psychotic symptoms.

The treatment course was complicated by deep vein thrombosis, a right segmental pulmonary embolus, hyponatremia, and a visual field cut. Following discharge from the hospital, Jonathan became increasingly anxious, irritable, and exhibited personality changes with family members. In his post discharge appointment with psycho-oncology psychiatry, he described symptoms of posttraumatic stress disorder (PTSD). He recalled the awake surgery and the sounds of the various instruments, specifically a surgical saw, while lying in a reclined position.

Since returning home from the hospital, he cannot tolerate laying back in his recliner, which leads him to re-experience his awake surgery, especially in the presence of any loud sounds from the television. He endorsed insomnia and occasional nightmares of the surgery and the ICU delirium experience. He also noted irritability and insomnia since starting on levetiracetam for seizure prophylaxis and worsening memory impairments. Given the visual field cut which did not abate, he incurred extreme difficulty with facial recognition and no longer was able to drive. In noting this, he described a loss of his identity, given his love of cars.

Just before the second surgery, his mother died unexpectedly. Jonathan had been very close to his mother, and she inspired him to follow his dream of becoming an attorney; she had also been his dedicated caregiver since his initial diagnosis. As his second surgery and hospital course immediately ensued following his mother’s death, he did not have the opportunity to process his grief, not to mention grieving for his own loss of identity.

It was apparent Jonathan was suffering from a complicated grief reaction, demoralization, symptoms of PTSD, and neurocognitive and functional impairments that required a multi-disciplinary approach. Working closely with neuro-oncology, the recommendation was to transition from levetiracetam, given its neuropsychiatric effects, to a mood stabilizing antiepileptic medication such as lamotrigine. Other psychopharmacological interventions included sertraline for anxiety and symptoms of PTSD and prazosin for nightmares. Referrals were made for neurocognitive rehabilitation, trauma informed therapy, grief and loss counseling, and a caregiver support group for patients with brain tumors.

Eventually, Jonathan’s symptoms of PTSD improved with both trauma informed therapy and medication interventions. Through neurocognitive rehabilitation, he was able to employ adaptation strategies that improved his memory recall, interpersonal communication, self-esteem, and sense of autonomy. In turn, his family learned to adapt to his specific needs, while feeling supported by caregiver support groups and services.

Discussion

At our institution, we are fortunate to have a family camp that is sponsored by the neuro-oncology department; it allows patients and their family members, medical, nursing, and support staff to engage in numerous activities, while enjoying respite outside the medical setting. This case illustrates the multiple and complex psychosocial stressors and neuropsychiatric sequalae inherent to the brain tumor population, which requires a concerted multidisciplinary approach and extensive resources to improve and maintain quality of life.

The 2 cases represent general clinical approaches to breast and CNS cancers. Accordingly, there are nuanced clinical approaches to other cancers, including hematologic-oncological, head and neck, lung, gastrointestinal, genitourinary, gynecological, prostate, neuroendocrine, sarcoma, and melanoma (see Selected Readings).

Conclusion

The overall cancer death rate has declined by 26% from 1991 to 2015, while the number of cancer survivors has increased. In 2016, there were an estimated 15.5 million cancer survivors in the United States, with projections of cancer survivorship expected to increase to 20.3 million by 2026.³

Given the marked upward trend in cancer survivorship, how will we meet the ideals of Dr Holland and the increased need for psychosocial care and quality of life measures? Improvements in cancer care continue an upward trajectory; however, psychosocial and quality of life measures are not always synchronous. In the words of Joseph Campbell, “You have to be willing to give up the life you planned, and instead, greet the life that is waiting for you.” To that end, our care and attention demands we help our patients “greet the life that is waiting,” by our unwavering pursuit of improved psycho-oncology research and clinical care.

Dr Kaplan is Associate Clinical Professor, and Director, Consultation Liaison Psychiatry Division, Department of Psychiatry and Behavioral Sciences at the University of California San Francisco (UCSF) Weill Institute for Neurosciences and Director of Psychiatry Oncology, Helen Diller Family, Comprehensive Cancer Center. He reports no conflicts of interest concerning the subject matter of this article.

References

1. Silver SM. Cancer care for the whole patient-a new institute of medicine report. J Oncol Pract. 2008;4:131.

2. Meyer F, Freeman MP, Petrillo L, et al. Armodafinil for fatigue associated with menopause: an open-label trial. Menopause. 2016;23:209-214.

3. National Cancer Institute. Cancer Statistics. 2018. https://www.cancer.gov/about-cancer/understanding/statistics. Accessed July 16, 2020.

SELECTED FURTHER READINGS

Breast Cancer

1. Akechi T, Momino K, Miyashita M, et al. Anxiety in disease-free breast cancer patients might be alleviated by provision of psychological support, not of information. Jpn J Clin Oncol. 2015;45:929-933.

2. Biglia N, Bounous VE, Susini T, et al. Duloxetine and escitalopram for hot flushes: efficacy and compliance in breast cancer survivors. Eur J Cancer Care (Engl). 2018;27.

3. Carlson LE, Tamagawa R, Stephen J, et al. Randomized-controlled trial of mindfulness-based cancer recovery versus supportive expressive group therapy among distressed breast cancer survivors (MINDSET): long-term follow-up results. Psychooncol. 2016;25:750-759.

4. Fang SY, Chang HT, Shu BC. The moderating effect of perceived partner empathy on body image and depression among breast cancer survivors. Psychooncol. 2015;24:1815-1822.

5. Freeman-Gibb LA, Janz NK, Katapodi MC, et al. The relationship between illness representations, risk perception and fear of cancer recurrence in breast cancer survivors. Psychooncol. 2017;26:1270-1277.

6. Jacob L, Kalder M, Kostev K. Incidence of depression and anxiety among women newly diagnosed with breast or genital organ cancer in Germany. Psychooncol. 2017;26:1535-1540.

7. Manne SL, Kashy D, Siegel SD, Heckman CJ. Group therapy processes and treatment outcomes in 2 couple-focused group interventions for breast cancer patients. Psychooncol. 2017;26:2175-2185.

8. Mens MG, Helgeson VS, Lembersky BC, et al. Randomized psychosocial interventions for breast cancer: impact on life purpose. Psychooncol. 2016;25:618-625.

9. Meyer F, Freeman MP, Petrillo L, et al. Armodafinil for fatigue associated with menopause: an open-label trial. Menopause. 2016;23:209-214.

Depression in Cancer Patients

1. Meyer F, Fletcher K, Prigerson HG, et al. Advanced cancer as a risk for major depressive episodes. Psychooncol. 2015;24:1080-1087.

2. Mulick A, Walker J, Puntis S, et al. Does depression treatment improve the survival of depressed patients with cancer? A long-term follow-up of participants in the SMaRT Oncology-2 and 3 trials. Lancet Psychiatry. 2018;5:321-326.

3. Sharpe M, Walker J, Holm Hansen C, et al. Integrated collaborative care for comorbid major depression in patients with cancer (SMaRT Oncology-2): a multicentre randomised controlled effectiveness trial. Lancet. 2014;384:1099-1108.

4. Sullivan DR, Mongoue-Tchokote S, Mori M, et al. Randomized, double-blind, placebo-controlled study of methylphenidate for the treatment of depression in SSRI-treated cancer patients receiving palliative care. Psychooncol. 2017;26:1763-1769.

5. Walker J, Hansen CH, Martin P, et al. Integrated collaborative care for major depression comorbid with a poor prognosis cancer (SMaRT Oncology-3): a multicentre randomised controlled trial in patients with lung cancer. Lancet Oncol. 2014;15:1168-1176.

General Psycho-oncology

1. Holland JC, Breitbart WS, Jacobsen PB, et al, Eds. Psycho-Oncology, 3rd ed. Oxford, UK: Oxford University Press; 2015.

Hematology Oncology

1. Amonoo HL, Massey CN, Freedman ME, et al. Psychological considerations in hematopoietic stem cell transplantation. Psychosomat. 2019;60:331-342.

2. Artherholt SB, Hong F, Berry DL, Fann JR. Risk factors for depression in patients undergoing hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2014;20:946-950.

3. Beglinger LJ, Duff K, Van Der Heiden S, et al. Incidence of delirium and associated mortality in hematopoietic stem cell transplantation patients. Biol Blood Marrow Transplant. 2006;12:928-935.

4. El-Jawahri AR, Vandusen HB, Traeger LN, et al. Quality of life and mood predict posttraumatic stress disorder after hematopoietic stem cell transplantation. Cancer. 2016;122:806-812.

5. Fann JR, Alfano CM, Burington BE, et al. Clinical presentation of delirium in patients undergoing hematopoietic stem cell transplantation. Cancer. 2005;103:810-820.

6. Fann JR, Hubbard RA, Alfano CM, et al. Pre- and post-transplantation risk factors for delirium onset and severity in patients undergoing hematopoietic stem-cell transplantation. J Clin Oncol. 2011;29:895-901.

7. Fann JR, Roth-Roemer S, Burington BE, et al. Delirium in patients undergoing hematopoietic stem cell transplantation. Cancer. 2002;95:1971-1981.

8. Jim HSL, Sutton SK, Small BJ, et al. Trajectories of quality of life after hematopoietic cell transplantation: secondary analysis of Blood and Marrow Transplant Clinical Trials Network 0902 data. Biol Blood Marrow Transplant. 2016;22:2077-2083.

9. Knight JM, Lyness JM, Sahler OJ, et al. Psychosocial factors and hematopoietic stem cell transplantation: potential biobehavioral pathways. Psychoneuroendocrinol. 2013;38:2383-2393.

10. Knight JM, Syrjala KL, Majhail NS, et al. Patient-reported outcomes and socioeconomic status as predictors of clinical outcomes after hematopoietic stem cell transplantation: a study from the Blood and Marrow Transplant Clinical Trials Network 0902 trial. Biol Blood Marrow Transplant. 2016;22:2256-2263.

11. Pawar DS, Molinaro JR, Knight JM, Heinrich TW. Toxicities of CAR T-cell therapy and the role of the consultation-liaison psychiatrist. Psychosomat. 2019;60:519-523.

12. Wood WA, Le-Rademacher J, Syrjala KL, et al. Patient-reported physical functioning predicts the success of hematopoietic cell transplantation (BMT CTN 0902). Cancer. 2016;122:91-98.

Neurocognitive

1. Cox LE, Ashford JM, Clark KN, et al. Feasibility and acceptability of a remotely administered computerized intervention to address cognitive late effects among childhood cancer survivors. Neurooncol Pract. 2015;2:78-87.

2. Gehring K, Patwardhan SY, Collins R, et al. A randomized trial on the efficacy of methylphenidate and modafinil for improving cognitive functioning and symptoms in patients with a primary brain tumor. J Neurooncol. 2012;107:165-174.

3. Janelsins MC, Kesler SR, Ahles TA, Morrow GR. Prevalence, mechanisms, and management of cancer-related cognitive impairment. Int Rev Psychiatry. 2014;26:102-113.

4. Wefel JS, Vidrine DJ, Veramonti TL, et al. Cognitive impairment in men with testicular cancer prior to adjuvant therapy. Cancer. 2011;117:190-196.

Neuroendocrine Tumors

1. Shi DD, Yuppa DP, Dutton T, et al. Retrospective review of serotonergic medication tolerability in patients with neuroendocrine tumors with biochemically proven carcinoid syndrome. Cancer. 2017;123:2735-2742.

Parenting and Family

1. Nilsson ME, Maciejewski PK, Zhang B, et al. Mental health, treatment preferences, advance care planning, location, and quality of death in advanced cancer patients with dependent children. Cancer. 2009;115:399-409.

2. Park EM, Deal AM, Check DK, et al. Parenting concerns, quality of life, and psychological distress in patients with advanced cancer. Psychooncol. 2016;25:942-948.

3. Siegel K, Karus DG, Raveis VH, et al. Depressive distress among the spouses of terminally ill cancer patients. Cancer Pract. 1996;4:25-30.

4. Weaver KE, Rowland JH, Alfano CM, McNeel TS. Parental cancer and the family: a population-based estimate of the number of US cancer survivors residing with their minor children. Cancer. 2010;116:4395-4401.

5. Yellen SB, Cella DF. Someone to live for: social well-being, parenthood status, and decision-making in oncology. J Clin Oncol. 1995;13:1255-1264.

6. Yopp JM, Park EM, Edwards T, et al. Overlooked and underserved: Widowed fathers with dependent-age children. Palliat Support Care. 2015;13:1325-1334.

Prostate Cancer

1. Prasad SM, Eggener SE, Lipsitz SR, et al. Effect of depression on diagnosis, treatment, and mortality of men with clinically localized prostate cancer. J Clin Oncol. 2014;32:2471-2478.

2. Roth AJ. Managing Prostate Cancer: A Guide to Better Living. New York: Oxford University Press; 2015.

3. Roth AJ, Weinberger MI, Nelson CJ. Prostate cancer: psychosocial implications and management. Future Oncol. 2008;4:561-568.

4. Taaffe DR, Newton RU, Spry N, et al. Effects of different exercise modalities on fatigue in prostate cancer patients undergoing androgen deprivation therapy: a year-long randomised controlled trial. Eur Urol. 2017;72:293-299.

Suicide in Cancer Patients

1. Fang F, Fall K, Mittleman MA, et al. Suicide and cardiovascular death after a cancer diagnosis. N Engl J Med. 2012;366:1310-1318.

2. Misono S, Weiss NS, Fann JR, et al. Incidence of suicide in persons with cancer. J Clin Oncol. 2008;26:4731-4738.

3. Walker J, Waters RA, Murray G, et al. Better off dead: suicidal thoughts in cancer patients. J Clin Oncol. 2008;26:4725-4730.

Symptom Management

1. Braun IM, Wright A, Peteet J, et al. Medical oncologists’ beliefs, practices, and knowledge regarding marijuana used therapeutically: a nationally representative survey study. J Clin Oncol. 2018;36:1957-1962.

2. Bruera E, Yennurajalingam S, Palmer JL, et al. Methylphenidate and/or a nursing telephone intervention for fatigue in patients with advanced cancer: a randomized, placebo-controlled, phase II trial. J Clin Oncol. 2013;31:2421-2427.

3. Navari RM, Qin R, Ruddy KJ, et al. Olanzapine for the prevention of chemotherapy-induced nausea and vomiting. N Engl J Med. 2016;375:134-142.

Therapies

1. Breitbart W, Rosenfeld B, Pessin H, et al. Meaning-centered group psychotherapy: an effective intervention for improving psychological well-being in patients with advanced cancer. J Clin Oncol. 2015;33:749-754.

2. Chambers SK, Occhipinti S, Foley E, et al. Mindfulness-based cognitive therapy in advanced prostate cancer: a randomized controlled trial. J Clin Oncol. 2017;35:291-297.

3. Cheung EO, Cohn MA, Dunn LB, et al. A randomized pilot trial of a positive affect skill intervention (lessons in linking affect and coping) for women with metastatic breast cancer. Psychooncol. 2017;26:2101-2108.

4. Houmann LJ, Chochinov HM, Kristjanson LJ, et al. A prospective evaluation of Dignity Therapy in advanced cancer patients admitted to palliative care. Palliat Med. 2014;28:448-458.

5. Kittelson S, Scarton L, Barker P, et al. Dignity therapy led by nurses or chaplains for elderly cancer palliative care outpatients: protocol for a randomized controlled trial. JMIR Res Protoc. 2019;8:e12213.