Resilience Matters: Mental Wellness Tied to Higher Immunotherapy Success in Advanced Non-Small Cell Lung Cancer

Physicians have long known there is a connection between mental health and physical health, but what was not recognized is that this anxiety can actually interfere with the outcome of certain cancer treatments. Most notably, emotional distress has a profound impact on the effectiveness of immunotherapy.

In a recent study published in Nature Medicine, researchers compared the outcomes of patients with non-small-cell lung cancer receiving immunotherapy to determine if emotional distress played a factor in their treatment outcome. They found patients without emotional distress had progression-free survival almost double that of patients suffering from emotional distress. Likewise, the objective response rate to immunotherapy was 46.8% for those with emotional distress, compared to 65% in those who did not suffer from this condition.

This data drives home the importance of early mental health screening and intervention to help improve patient outcomes.

For insight into this crucial mental/physical health connection, we turned to Shiyao Wang, MD, of the Cleveland Clinic Cancer Institute's Department of Palliative and Supportive Medicine, who recently co-authored a paper in Translational Lung Cancer Research about this topic. A psychiatrist by training, Dr. Wang did his fellowship in consultation-liaison psychiatry at Thomas Jefferson University Hospital. He now works as a psychosocial oncologist at Cleveland Clinic Cancer Institute.

CQD: Thank you for taking the time to talk with us today. First, can you tell us a bit about what your team does?

SW: We offer comprehensive psychological and psychiatric mental health support for patients receiving cancer care at Cleveland Clinic. Our team includes two full-time psychosocial oncologists, three cancer psychologists as well as a psychologist in Florida. We also have a new psychologist starting at our site in Akron.

CQD: What sparked your interest in this study?

SW: The reason I got interested in this study is because we now know that cancer treatment outcomes will be negatively impacted if emotional distress is not properly recognized and treated. This opens the door for mental health professionals to talk with medical oncologists about the importance of treating mental health issues.

CQD: Can you explain specifically how emotional distress disrupts the effectiveness of immunotherapy?

SW: Yes, The whole point of immunotherapy is to make the immune system more robust to target cancer. When patients are going through distress, their HPA (hypothalamic-pituitary-adrenal) axis is dysregulated. Their CD-8 cells and NK cells, which are in charge of killing cancer cells, are less active.

People having chronic stress tend to have dysregulated sleep and decreased appetite and are less likely to follow recommended lifestyle modifications, which further impacts immune activity, so overall, their immunotherapy outcome appears less robust.

CQD: How do you define emotional distress? Wouldn't most people with cancer have this?

SW: Yes, but it's on a spectrum. Some people have milder emotional distress that is proportional to cancer diagnosis and treatment. They may have better coping skills and social supports and have learned ways to handle stress. In those cases, they may go through a shorter period of distress and then quickly focus on their care plan and how to move forward versus other people who feel more overwhelmed and have a hard time managing this in an effective way.

Cognitive functioning comes into this as well, because when we're under duress, it's harder to think clearly, be motivated to make your next recommended appointment or remember to take medications, for example. That makes the whole task of receiving cancer treatment more challenging.

CQD: Were there other findings in the study that stood out to you?

SW: Yes, the researchers found that poorer outcomes for those with emotional distress were universal across all subgroups, so no matter the patient's age, gender, histology, smoking status or degree of metastases, we see a consistent negative outcome when patients are experiencing emotional distress. This data reinforces the point that this is something we need to screen for.

CQD: Your paper mentioned that there's a mutually reinforcing relationship between cancer and emotional distress. Can you explain what that means?

SW: Getting a cancer diagnosis is inherently very overwhelming and stress inducing. When patients are going through this distress, it can sometimes get in the way of effectively engaging in their cancer treatment. If a person is too depressed or anxious to move forward and adhere to treatment recommendations, we tend to see worse outcomes and more suffering, which is likely to perpetuate anxiety and depression, so it’s a two-way street.

Coming to the hospital every single day for 35 days of radiation, for example, is very stressful and requires a lot of motivation, planning and coordination with the patient’s care team and family. That’s especially true for people who still have to work and take care of their family. Having all that stress can impact their ability to concentrate, impact their motivation and affect their desire to further engage with care.

In those cases, we talk about their values, identify their strengths and discuss how to support them and keep them going through this tough process.

CQD: What are the best ways to identify patients in emotional distress?

SW: I see more oncologists including mental health symptoms in their assessment, which is a very good sign. We have the General Anxiety Disorder (GAD-7) and Patient Health Questionnaire (PHQ-9), which are scoring tools to help identify patients who are more vulnerable and may suffer from mental health symptoms. From there, a comprehensive psychosocial assessment may be beneficial to identify the existence and severity of mental distress. The social work team at Cleveland Clinic Cancer Institute works closely with the oncology and mental health teams in this process.

CQD: Can you share how the Clinic helps patients with cancer in these situations?

SW: The mental health team at Cleveland Clinic Cancer Institute takes referrals from oncologists, palliative care providers and sometimes inpatient psychiatrists. We assess what the patient’s needs are and provide recommendations to manage symptoms and help the patient achieve their goals.

Not everyone who's experiencing emotional distress needs to see a psychiatrist. For example, someone may be having existential questions like what's the point of going through chemo when I feel worse every day? In those cases, potentially talking with a cancer psychologist will help them process and accept their cancer diagnosis, identify their coping styles and skills and understand what their goals and values are. In other cases, there are biological factors that precipitate and/or perpetuate patient’s mental health symptoms, which can be intervened with pharmacological treatment.

CQD: What other types of supports does Cleveland Clinic offer?

SW: Through a good assessment, we can find out what is most beneficial for each patient. In some cases, housing, financial burdens and/or employment disruption are adding emotional distress. For example, for patients who live outside the area and are at Cleveland Clinic Cancer Institute for treatment, our social workers can help them find temporary lodging or provide financial assistance.

The Palliative and Supportive Care Teams provide symptomatic management for patients going through cancer, including pain, constipation, fatigue, nausea and diarrhea, and facilitate goal-of-care discussions. Cleveland Clinic Cancer Institute also offers patients and caregivers supportive services such as yoga, meditation, massage therapy as well as art and music therapy. There are other supporting services in the community that we often refer patients to, such as the Gathering Place and 4^th Angel program. They provide additional services to patients and their family, such as group therapy for certain types of cancer and peer support via a mentorship program.

CQD: What role does your team play in educating patients about the importance of mental health in their cancer care?

SW: For many patients, we are the first contact they've ever had with a mental health professional. Being able to help patients understand emotions and feelings they are going through is common. Working with them from an oncology care standpoint can be very helpful to de-stigmatize mental health services overall. Getting our team involved as part of the treatment team can be very beneficial for patients' quality of life, overall well-being and treatment outcome.