Cognitive Behavioral Effects on Sleep, Pain, and Cytokines in Gynecologic Cancer

Gynecologic cancers cause substantial morbidity and mortality among women. Developing,
implementing, and disseminating interventions that reduce morbidity and mortality secondary
to gynecologic cancers are a public health priority. To the extent that psychological factors
may influence quality of life and tumor biology among women with gynecologic cancers,
psychological interventions may represent an important adjunct to standard clinical care in
this population. Among individuals with cancer, there is emerging evidence that stressors and
psychological responses to stressors activate central and peripheral stress systems,
resulting in downstream effects on the tumor microenvironment, e.g.
hypothalamic-pituitary-adrenal (HPA) axis dysregulation, inflammatory/growth factor
upregulation that may favor tumorigenesis. Little is known about whether psychological
interventions may modulate biobehavioral factors that may promote tumorigenesis among women
with gynecologic cancer. This is a significant gap in the literature. Sleep quality, pain,
and mood are three patient-centered outcomes that may represent important intervention
targets for women with gynecologic cancers, as insomnia, pain, and negative mood states are
(1) prevalent and (2) have been associated with HPA dysregulation and inflammatory/growth
factor upregulation in this population in empirical research. This study will examine
cognitive behavioral therapy (CBT) intervention effects on patient centered and physiological
outcomes among women with gynecologic cancers undergoing adjuvant chemotherapy. Grounded
within the Central Arousal Theory of Stress (CATS) and a biobehavioral model of tumor
biology, the central hypothesis is that a CBT intervention targeting insomnia and pain will
(a) improve nighttime sleep patterns, pain, and negative mood states, and (b) reduce cortisol
levels, normalize daytime cortisol rhythm, and reduce proinflammatory/proangiogenic cytokine
levels in women with gynecologic cancers. The multidisciplinary team will have
research/clinical experience in psycho-oncology, psychoneuroimmunology (PNI), behavioral
sleep medicine, pain, reproductive immunology, and gynecologic oncology. The research study
is innovative in that it will (1) combine empirically-supported CBT techniques for insomnia
and pain into a multicomponent intervention tailored for women with gynecologic cancers, and
(2) examine CBT effects on central sensitization of pain among individuals with cancer using
quantitative sensory testing (QST). The results of this research will be significant to
public health initiatives, because although gynecologic cancers are among the leading causes
of cancer-related death among women, there is a paucity of research examining the effects of
psychosocial interventions on patient-centered and physiological outcomes in this population.

Inclusion Criteria

- Women 18 and older scheduled and/ or have recently had a surgical resection,
debulking, or cytoreduction for gynecologic malignancies for which adjuvant treatment
or chemotherapy is the standard of care. Most of these cases are expected to be: (i)
epithelial ovarian cancer, any stage, any grade, (ii) epithelial endometrial cancer,
clear cell, papillary serous, or carcinosarcoma morphologies; any stage; any grade,
(iii) epithelial endometrial cancer, endometrioid morphology; any stage any grade,
(iv) fallopian tube cancer, any stage, any grade, (v) peritoneal cancer, any stage,
any grade, or (vi) squamous cell carcinomas of the female genital tract (uterus,
cervix, vulva, and vagina), any stage, any grade, in situ, or (vii) borderline ovarian
tumors.

- Endorsement of any of the following sleep related complaints in the month prior to
enrollment (at pre- or post-surgery): difficulty initiating sleep, difficulty
maintaining sleep, waking up too early, or sleep that is chronically nonrestorative or
poor in quality.

- During the two weeks of sleep evaluation at the post-surgical timepoint: sleep
diary/clinical interview confirmed insomnia (e.g., sleep onset or awake time during
the night > 30 minutes) at least 3 nights per week; or, sleep diary/clinical interview
confirmed insomnia on 1 to 5 nights across the two weeks of evaluation plus Sleep
Efficiency on Pittsburgh Sleep Quality Index at post-surgery < 85%.

- Presence of daytime dysfunction due to insomnia (mood, cognitive, social, or
occupational impairment) at post-surgery.

- Able to read and understand English.

- Willing to undergo randomization.

Exclusion Criteria:

- Unable to provide informed consent.

- Current, severe, uncontrolled psychopathology that would make randomization to
conditions unethical.

- Past or current diagnosis of Bipolar Disorder or seizure disorder that would prevent
the safe implementation of sleep restriction techniques.

- Participation in Cognitive Behavioral Therapy or any nonpharmacological treatment for
sleep outside of the current study.

- Sleep apnea or periodic limb movement disorder (PLMD).

- Physician estimated survival less than 6 months.