Posttraumatic stress disorder (PTSD) is a psychiatric disorder that may occur in people who have experienced or witnessed a traumatic event such as a natural disaster, war, rape, or who have been threatened with death, sexual violence, or serious injury. While often overlooked, a serious illness like cancer may also lead to PTSD. In fact, the most recent edition of the Diagnostic and Statistical Manual for Mental Disorder (5th edition; DSM 5) identifies a “life-threatening illness or debilitating medical condition” as a possible traumatic event that may lead to either posttraumatic stress (PTS) symptoms or full PTSD.[1]

While cancer is one such illness that may lead to the development of PTS or PTSD, it is inherently different from other nonmedical traumatic events.[2] In the context of cancer, PTS symptoms may appear after being informed of the diagnosis (i.e., either due to the traumatic nature of being diagnosed with a chronic or life-limiting illness, or due to the manner in which diagnostic information is shared with or learned by the patient), or in response to cancer progression and/or treatment side effects, complications, disfigurements, or dysfunctions, or other aversive medical experiences related to cancer treatment.

The potentially protracted and multifaceted nature of cancer warrants an astute awareness and understanding of how PTS may present in people living with cancer, and how to best respond to the physical and psychological symptoms for improved outcomes.

Posttraumatic Stress Disorder (PTSD) and Cancer
The prevalence of PTS symptoms among patients with cancer is well documented, yet due to inconsistent definitions, applications of varying diagnostic criteria, and few longitudinal investigations, its trajectory is poorly understood and it often goes unrecognized.[3] It is clear nonetheless that PTS can impair patients’ quality of life and health status. Cancer-related PTS symptoms include nightmares and sleep disturbances, flashbacks and rumination about the diagnosis and treatment, and cognitive and behavioral avoidance of cancer-related stimuli. Nightmares may be so debilitating that patients have difficulty falling or staying asleep, and flashbacks to the diagnosis can overwhelm patients for days at a time. As a result, cognitive and behavioral avoidance of cancer-related cues is common and can impair patients’ continued engagement in necessary medical care.

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While some comprehensive cancer centers routinely screen for psychological distress, PTSD is frequently overlooked due to lack of awareness and absence of affordable, accessible treatment solutions. Additionally, the highly physiological nature of PTS, in combination with its under-recognition, may result in psychological symptoms being misinterpreted as additional physical symptoms of cancer. Unless clinicians are sensitive to the possibility of PTSD, there is a likelihood of favoring treatment for the most obvious physical symptoms that result from psychological symptoms (e.g., racing heart). Failure to identify and address PTS can be especially problematic as it can lead to negative health consequences including a dysregulated neuroendocrine stress response, impaired immunity, cognitive dysfunction, chronic pain, depression, and poor quality of life.[4][5] PTS is linked to a higher incidence of additional medical diagnoses even when controlling for the nature of the trauma, the individual’s health perception, daily stress, health behaviors, and co-occurring psychiatric disorders.

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PTSD and Patients with Blood Cancers
Patients diagnosed with acute myeloid leukemia (AML), and who undergo induction chemotherapy, are one group at high risk for PTS and PTSD. AML is characterized by sudden onset, intensive treatment, considerable morbidity and mortality, and a dramatic course and poor prognosis, with a median survival of six weeks without treatment. Individuals affected require immediate hospitalization to initiate intensive induction chemotherapy. This initial treatment typically lasts at least three weeks and is usually associated with toxic effects including severe stomatitis, nausea, and bone marrow depression, with life-threatening pancytopenia-related symptoms such as bleeding or sepsis. Although physical symptoms often improve after treatment completion, psychosocial distress persists over longer periods of time. Patients with AML describe the diagnosis as dramatic and shocking, a “whirlwind” or “like getting hit by a truck that you didn’t see coming.”[6]

The diagnosis and immediate initiation of treatment involve a sudden removal of patients from all aspects of their normal life, and the inpatient induction chemotherapy requires patients to leave that life behind, with notice of only hours or days, for a period of three to four weeks. In a qualitative study focused on the analysis of patients’ narratives about the initial diagnosis of acute leukemia (AL) and hospitalization for induction chemotherapy, one patient describes their experience as, “You’re kind of in shock. I mean I went to the emergency unit, they were trying to figure out what was wrong with me. I didn’t pack a bag or anything like that. I wound up staying there overnight and being shipped to this hospital. [I] didn’t see my apartment for months. They just picked me up and took me, took my life away.”[6]

It is therefore not surprising that this is a group at high risk for PTS/PTSD. Persisting or progressing PTSD symptoms affect a significant portion of AML patients [7][8], and are exacerbated if such patients go on to receive a hematopoietic stem cell transplant (HSCT).[9][10][11]

PTSD, Blood Cancers, and Transplant
As prior work has demonstrated, soon after diagnosis or relapse, PTS symptoms may be found in one-third of patients with various ALs, lymphocytic and promyelocytic leukemias in addition to AML. [12][13] This symptom burden related to AL and its treatment is comparable with that in patients with metastatic cancer.[14] [15] Many such patients require HSCTs as part of their treatment, and these transplants are also a risk factor for PTS/PTSD. One such patient, who was diagnosed with AML in 2012 and told he had a year to live, is another strong example of the severe disruption to life and psychological distress that can accompany a leukemia diagnosis. While he originally received outpatient chemotherapy, he was in and out of the hospital for several 30-day stays, including one for a failed HSCT. He describes his life following diagnosis as taking “a rapid downward turn.” He says, “ It was completely unexpected. I thought I just had a bad virus. I was fully employed and an active runner; I had always been in good health. But that all stopped suddenly.” Going on to describe the emotional impact he says, “I couldn’t have been more depressed. Especially since I had to undergo chemo infusions, blood transfusions, weekly platelets, and extensive hospital stays until it was time for my bone marrow transplant. The transplant ultimately failed after only six-months though and I had to undergo the same process all over again. Psychologically, it was extremely hard to accept that this happened to me, turning my life upside down.”[16]

Around 20,000 cancer patients undergo HSCT annually, with the goal to achieve long-term remission or cure. While a worthy goal, and as described above, HSCT is particularly physically and psychologically taxing, involving social isolation and heightened risk of infection and death. The life-threatening nature of HSCT – combined with required social isolation – makes it a prime example of a cancer-related trauma exposure. Six-months following allogeneic or autologous HSCT, recipients reported moderate to severe symptoms of PTS including re-experiencing (39%), avoidance (33%), and hyperarousal (48%).[11] PTS symptoms post-HSCT may be chronic, and have been identified in around 37% of lymphoma survivors over seven years from diagnosis, and 41% of HSCT survivors reported avoidance, nightmares, and heightened arousal up to ten years following transplant.[17] Strikingly, cancer survivors who receive HSCT as part of an intensive treatment course are at greatest risk for PTSD, with a 50% chance of lingering PTSD symptoms.[18] Such PTSD results in significant distress, impairs health outcomes, decreases quality of life, and contributes to higher healthcare costs.

Cognitive Behavioral Therapy and the Future of PTSD Treatment in Cancer
The concept of PTSD itself implies that the genuinely threatening event is in the past. Existing therapeutic packages for PTSD implicitly or explicitly begin with Judith Lewis Herman’s theory that safety must be established before more active treatments can begin.[19] However, a cancer diagnosis represents an ongoing threat that requires participation in clinical encounters that, through their inconvenience, expense, pain, and discomfort, may repeatedly reinforce the significance of that threat and therefore such “safety” is not always possible in the setting of cancer. Cancer in effect causes exposure to traumatic stimuli without “safety” (i.e., absence of cancer), and this complicates not only the use of existing models of treatment but also possibly the use of the diagnostic category of PTSD itself.[20] Perhaps not surprisingly, avoidance of all reminders of cancer and/or related traumatic stimuli is common among patients and is potentially the most clinically significant set of symptoms due to its effect on adherence to treatment. Indeed, the association between such PTSD symptoms and avoidance of reminders of the trauma (e.g., the cancer center itself, the oncologist, certain treatment-related stimuli) underscores the urgency of addressing PTSD in this group. As such, targeting sustained acute distress during active treatment and prior to the development of PTS symptoms might have the greatest potential to affect adherence and cancer outcomes.[21]

Despite the ongoing threat of cancer, existing research demonstrates that Cognitive Behavioral Therapy (CBT) has been effective in addressing PTSD and related distress arising in the cancer setting. Components of CBT generally include psychoeducation about distress and PTSD after cancer, breathing and relaxation training, imaginal and in vivo exposure to cancer-related cues, cognitive restructuring, behavioral activation/activity scheduling, enhancement of social support through training in communication skills, relapse preventions, and generalizability of skills.[22][23]

While effective therapeutic technologies exist, very few patients receive PTSD-targeted psychosocial support. This is due, in part, to the limited availability of psychosocial oncology providers, a lack of training in CBT for PTSD among psychosocial oncology providers, and the challenges patients face in engaging in psychosocial care while experiencing severely debilitating physical symptoms. These limitations, combined with the general under-identification of PTSD symptoms among patients with cancer, have led to a significant proportion of distressed patients with cancer not receiving necessary psychosocial care, and ultimately experiencing intensifying distress and psychiatric morbidity. As such, there is an urgent need for the development and dissemination of feasible, acceptable, and efficacious treatment packages for PTSD-related distress in cancer that do not add further burden to patients or our already overtaxed healthcare system.

Fortunately, for patients and providers alike, the treatment landscape for cancer-related distress, including PTSD, is evolving. In addition to time-tested behavioral health interventions and the acceleration of virtual health visits, innovative cancer-specific prescription digital therapeutics (PDTs) are emerging. Based on clinically proven and validated interventions, PDTs are software-based tools being developed for a range of serious conditions, including cancer. These new therapeutics have the potential to expand healthcare providers’ set of tools, including the capacity to more effectively treat PTSD for patients diagnosed with AML.

For many patients, AML is not only a life-threatening disease but one that causes significant psychological effects. As AML World Awareness Day approaches in April, I encourage health care providers to be aware of the interrelatedness of the AML illness journey and PTSD symptoms. A holistic approach, addressing not only the physical but the psychological aspects of disease, will lead to greater quality of life and improved health outcomes for patients living with AML.

Disclosures:
The patients mentioned in this editorial are not affiliated with the author or Memorial Sloan Kettering Cancer Center. Quotes are as referenced by the citation or provided through a patient advisor relationship with Blue Note Therapeutics, a company dedicated to easing the burden of cancer and improving outcomes.

The author has a consulting and financial relationship with Blue Note Therapeutics, Inc.; Blue Note provided financial and editorial assistance to this article.

Reference
[1] American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 5th ed. Washington, DDC, American Psychiatric Association, 2013.
[2] Kangas M, Henry JL, Bryant RA. Posttraumatic stress disorder following cancer, a conceptual and empirical review. Clin Psychol Rev 2022; 22: 499:524.
[3] Cordova MJ, Riba MB, Spiegel D. Post-traumatic stress disorder and cancer. The lancet Psychiatry. 2017; 4(4):330-338. doi:10.1016/s2215-0366(17)30014-7.
[4] D’Andrea W, Sharma R, Zelechoski AD, Spinazzola JJJotAPNA. Physical health problems after single trauma exposure: When stress takes root in the body. 2011; 17(6):378-392.
[5] Pacella ML, Hruska B, Delahanty DL. The physical health consequences of PTSD and PTSD symptoms: A meta-analytic review. Journal of Anxiety Disorders. 2013; 27(1):33-46. doi:https://doi.org/10.1016/j.janxdis.2012.08.004.
[6] Nissim R, Zimmermann C, Minden M, Rydall A, Yuen D, Mischitelle A, Gagliese L, Schimmer A, Rodin G. Abducted by the illness: a qualitative study of traumatic stress in individuals with acute leukemia. Leuk Res. 2013 May;37(5):496-502. doi: 10.1016/j.leukres.2012.12.007. Epub 2013 Jan 24. PMID: 23352641; PMCID: PMC3808345.
[7] Rodin G, Yuen D, Mischitelle A, Minden MD, Brandwein J, Schimmer A, et al. Traumatic stress in acute leukemia. Psychooncology. Nov 13.2011 epub ahead of print.
[8] Koenigsmann M, Koehler K, Regner A, Franke A, Frommer J. Facing mortality: a qualitative in-depth interview study on illness perception, lay theories and coping strategies of adult patients with acute leukemia 1 week after diagnosis. Leuk Res. 2006; 30(9):1127–34. [PubMed: 16458356]
[9] Danhauer, SC., Russell, GB., Tedeschi, RG., Jesse, MT., Vishnevsky, T., Daley, K., et al. A longitudinal investigation of posttraumatic growth in adult patients undergoing treatment for acute leukemia. J Clin Psychol Med Settings. Jun 28. 2012 http://dx.doi.org/10.1007/s10880-012-9304-5 [epub ahead of print online first™]
[10] Xuereb MC, Dunlop R. The experience of leukaemia and bone marrow transplant: searching for meaning and agency. Psychooncology. 2003; 12(5):397–409. [PubMed: 12833554]
[11] El-Jawahri AR, Vandusen HB, Traeger LN, Fishbein JN, Keenan T, Gallagher ER, Greer JA, Pirl WF, Jackson VA, Spitzer TR, Chen YB, Temel JS. Quality of life and mood predict posttraumatic stress disorder after hematopoietic stem cell transplantation. Cancer. 2016;122(5):806-12. Epub 2015/12/10. doi: 10.1002/cncr.29818. PubMed PMID: 26650840; PMCID: PMC4788001.
[12] Depression and hopelessness in patients with acute leukemia: the psychological impact of an acute and life-threatening disorder – Galina Gheihman1, Camilla Zimmermann2,3,4, Amy Deckert2, Peter Fitzgerald2,5, Ashley Mischitelle2, Anne Rydall2.
[13] Rodin G, Yuen D, Mischitelle A, et al. Traumatic stress in acute leukemia. Psycho-Oncology 2013;2:299–307.
[14] Zimmermann C, Yuen D, Mischitelle A, et al. Symptom burden and supportive care in patients with acute leukemia. Leuk Res 2013;37:731–736.
[15] Lo C, Zimmermann C, Rydall A, et al. Longitudinal study of depressive symptoms in patients with metastatic gastrointestinal and lung cancer. J Clin Oncol 2010;28:3084–3089.
[16] Deidentified Patient. Email to Blue Note Therapeutics Representative. Jan. 10. 2022.
[17] El-Jawahri A, Traeger L, Greer JA, VanDusen H, Fishman SR, LeBlanc TW, Pirl WF, Jackson VA, Telles J, Rhodes A, Li Z, Spitzer TR, McAfee S, Chen YA, Temel JS. Effect of inpatient palliative care during hematopoietic stem-cell transplant on psychological distress 6 months after transplant: Results of a randomized clinical trial. J Clin Oncol. 2017;35(32):3714-21. Epub 2017/09/20. doi: 10.1200/JCO.2017.73.2800. PubMed PMID: 28926288; PMCID: PMC5675739.
[18] Smith SK, Zimmerman S, Williams CS, Preisser JS, Clipp EC. Post-traumatic stress outcomes in non-Hodgkin’s lymphoma survivors. J Clin Oncol. 2008 Feb 20;26(6):934-41. doi: 10.1200/JCO.2007.12.3414. PMID: 18281667; PMCID: PMC3025533.
[19] Trauma and Recovery: The Aftermath of Violence–from Domestic Abuse to Political Terror by Judith Herman (Author).
[20] Psycho-Oncology 4th Edition by William Breitbart (Editor), Phyllis Butow (Editor), Paul Jacobsen (Editor), Wendy Lam (Editor), Mark Lazenby (Editor), Matthew Loscalzo (Editor), pg 369.
[21] Psycho-Oncology 4th Edition by William Breitbart (Editor), Phyllis Butow (Editor), Paul Jacobsen (Editor), Wendy Lam (Editor), Mark Lazenby (Editor), Matthew Loscalzo (Editor), pg 369 (Intervention, Psychotherapy section).
[22] Kangas M, Milross C, Taylor A, Bryant RA. A pilot randomized controlled trial of a brief early intervention for reducing posttraumatic stress disorder, anxiety and dep Conclusion: Findings indicate that the early provision of psychotherapy has utility in reducing PTSD, anxiety and depressive symptoms, and preventing chronic psychopathology in distressed HNC patients.Psychooncology. 2013 Jul;22(7):1665-73. doi: 10.1002/pon.3208. Epub 2012 Oct 8. PMID: 23042612.
[23] DuHamel KN, Mosher CE, Winkel G, Labay LE, Rini C, Meschian YM, Austin J, Greene PB, Lawsin CR, Rusiewicz A, Grosskreutz CL, Isola L, Moskowitz CH, Papadopoulos EB, Rowley S, Scigliano E, Burkhalter JE, Hurley KE, Bollinger AR, Redd WH. Randomized clinical trial of telephone-administered cognitive-behavioral therapy to reduce post-traumatic stress disorder and distress symptoms after hematopoietic stem-cell transplantation. J Clin Oncol. 2010 Aug 10;28(23):3754-61. doi: 10.1200/JCO.2009.26.8722. Epub 2010 Jul 12. PMID: 20625129; PMCID: PMC2917309. Conclusion: A brief, telephone-administered CBT intervention developed for HSCT survivors is an efficacious treatment for reducing illness-related PTSD symptoms and general distress.

Featured image:  Stressed Woman/Stressed female patients. Photo courtesy: Mismiba Tinashe Madando / Pixabay© . This file is made available under the Creative Commons CC0 1.0 Universal Public Domain Dedication.

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