Mindfulness practice reduces cortisol blunting during chemotherapy: A randomized controlled study of colorectal cancer patients

Abstract

Background

The objective of this randomized clinical experiment was to test the influence of a mindfulness meditation practice, when delivered during one session of active chemotherapy administration, on acute salivary cortisol response as a marker of the neuroendocrine system activity in cancer patients.

Methods

A mindfulness, attention control, or resting exposure was assigned to N=57 English- or Spanish- speaking colorectal cancer patients at one county oncology clinic and one university oncology clinic at the start of chemotherapy. Four saliva samples were collected at the start of chemotherapy and at subsequent 20-minute intervals during the first 60 minutes of chemotherapy. Self-report on biobehavioral assessments post-chemotherapy included distress, fatigue, and mindfulness.

Results

Area under the curve analysis (AUC_I and AUC_B) denoted a relative increase in cortisol reactivity in the mindfulness group after adjusting for biological and clinical measures (β=123.21, p=.03), indicating reduced acute cortisol blunting. More than twice as many patients in the mindfulness group as compared to controls displayed a cortisol rise from baseline to 20 minutes (69% vs. 34%, p=.02). AUCi values were uncorrelated with biobehavioral measure scores although mindfulness scores were inversely correlated with fatigue (r=−.46, p<.01) and distress (r=−.54, p<.01) scores.

Conclusions

Findings suggest that a mindfulness practice during chemotherapy can reduce blunting of neuroendocrine profiles typically observed in cancer patients. Implications include support for the use of mindfulness practice in integrative oncology.

Receiving a diagnosis of cancer and experiences of medical treatment present a threat to self and involve major life role modifications that can be overwhelming for the patient. To illustrate, up to 43% of patients with cancer report significant distress.¹ Patients with cancer endure physical and emotional events during and after treatment that can repeatedly activate a stress response, which involves the mobilization of the biological resources needed to cope with a demand or threat.^2,3 When the brain detects a significant demand, the hypothalamus produces corticotropin-releasing hormone (CRH), which stimulates its anterior pituitary to secrete adrenocorticotropic hormone (ACTH) to trigger the adrenal glands atop the kidneys to release the corticosteroid hormone cortisol.^4,5 Chronic activation of this system in patients with cancer, especially those with greater disease severity, is found to be associated with hypothalamic–pituitary–adrenal (HPA) axis dysregulation, mostly blunting of diurnal cortisol rhythm.^6–9 Longitudinal observational studies show that a blunted cortisol response in cancer survivors predicts disease progression and decreased survival time in breast, lung, ovarian, and renal cell carcinoma patients, after adjusting for important clinical and demographic characteristic.^10–13 These findings in cancer research align with the findings from various other fields showing cortisol blunting after chronic stress exposure.^14–16

A smaller group of studies have specifically examined the blunting of acute cortisol reactivity in cancer patients and survivors. Giese-Davis et al.¹⁷ administered a standardized stressor test (i.e., Trier Social Stress Test) to metastatic breast cancer patients and found acute cortisol reactivity to be blunted for these cancer patients relative to a non-cancer comparison group at risk for cardiovascular disease. The authors interpreted this as support for HPA axis hyporesponsivity in advanced cancer patients. Bower et al.¹⁸ also observed blunted salivary cortisol reactivity to the TSST among fatigued relative to non-fatigued breast cancer survivors. Only one study we are aware of has examined the cortisol reactivity elicited from engaging in clinically prescribed activities. Porter et al.¹⁹ conceptualized a mammography exposure as an acute stressor among breast cancer survivors. The selection of this exposure was relevant since mammography is often noted as one of the most salient triggers of recurrence fears in cancer survivors, and women without a history of breast cancer generally do not experience significant distress when undergoing routine mammography screening.²⁰ The Porter study showed that breast cancer survivors had blunted cortisol reactivity to an acute cancer-related stressor (mammography) in the years following completed treatment. The authors suggested that blunting might be caused by repeated physiological and psychological efforts by survivors to cope that resulted in fatigue and an inability to mount new acute responses to demand. It remains unknown if blunting of acute reactivity in cancer patients can be modified through intervention.

Mindfulness practice represents a novel learning experience founded on stress arousal reduction by engaging attention and awareness to bodily sensations and experiences without judgment or reactivity.²¹ The process of mindfulness is commonly defined as ‘the awareness that emerges through paying attention on purpose, in the present moment, and nonjudgmentally to the unfolding of experience moment by moment’.²² Programs that aim to cultivate mindfulness, such as the widely disseminated Mindfulness-Based Stress Reduction (MBSR) program,²² are available in some major cancer treatment centers across the nation²³ and empirical reviews have demonstrated their utility for attenuating subjective states of cancer-related symptoms.^24,25 For context, MBSR and related programs are housed within the broader medical models of mind-body medicine and integrative oncology.^26–28 We have previously observed that a significant proportion of colorectal cancer patients and survivors use integrative health modalities alongside conventional treatment.²⁹

Although the current literature is limited to a few studies that examine different diseases, preliminary finding suggest that mindfulness practice can influence cortisol profiles in cancer survivors (see review³⁰). For example, Carlson and colleagues et al.³¹ conducted a multisite, randomized controlled trial and assigned distressed breast cancer survivors to a mindfulness practice intervention, supportive-expressive group therapy, or a brief stress management control condition. Intent-to-treat analyses indicated that diurnal cortisol slopes were maintained in the mindfulness and group support condition while the control group slope showed cortisol blunting. Women in the mindfulness group also reported significantly less stress symptoms than women in either the support or control group. A separate pre-post, within-subjects study of breast and prostate cancer patients observed that the MBSR program was associated with a shift toward greater cortisol decline in the afternoon (less blunting) and this change was significantly associated with improved overall global quality of life.³² Taken together, this initial evidence suggests that mindfulness practice may protect against cortisol blunting in cancer patients and survivors when assessed at the level of diurnal rhythm.

The purpose of this randomized controlled experiment was to examine changes in cortisol reactivity among colorectal cancer patients during the first hour of chemotherapy infusion across a mindfulness exposure versus control to ascertain potential changes in cortisol blunting as the primary outcome. The impact of mindfulness practice during chemotherapy on physiological processes relevant to cancer is unexplored, and no study among cancer patients to date we are aware of has assessed cortisol at multiple time points across chemotherapy infusion. Our primary research question queried if mindfulness practice could awaken cortisol reactivity as a counter to blunting that is previously observed in cancer patients and survivors. Our thinking on the engagement of HPA axis activity during mindfulness practice was guided by literature on neuroendocrine response to novel learning exposures and states of eustress.^33–36 As such, we hypothesized that exposure to mindfulness practice, as a novel learning in attention and awareness to somatosensory states at the start of chemotherapy, would yield a relative increase in acute cortisol reactivity. Our exploratory aim was to test for significant associations between cortisol reactivity levels and self-report of biobehavioral factors (i.e., distress, fatigue, and mindfulness).

Method

Participants and Procedures

The experimental design was a two-site randomized, controlled study with group intervention exposures and cortisol assessments occurring during an active chemotherapy session. Enrolled participants were N=57 English- or Spanish-speaking adult colorectal cancer (CRC) patients receiving an adjuvant chemotherapy session at a county hospital oncology clinic or a university hospital oncology clinic, both located in East Los Angeles. Potential recruits were identified via referral made by the site’s attending oncologist. When a patient expressed interest in the study, the project staff scheduled a screening session and provided a detailed description of the study. Eligible recruits provided written informed consent prior to study enrollment. The informed consent process reviewed issues of confidentiality, the patient's right to refuse participation at any time, time commitments, and potential risks as well as benefits to participation. Recruits were eligible if they were 18 to 89 years of age, diagnosed with colorectal cancer, scheduled for a chemotherapy appointment, and willing to give informed consent, and were ineligible if their oncologist thought the patient too ill to participate or if the patient lacked proficiency in English or Spanish. The University of Southern California Institutional Review Board and Clinical Investigators Support Office approved all study procedures (registry #NCT02057991). HIPPA clearance was also obtained from medical record and chart reviews.

After obtaining informed consent, recruits were enrolled in the study and research staff met with each participant to collect demographics from a brief, self-report measure. Medical data were also obtained using a brief questionnaire in which treating oncologists reported patients’ diagnosis. This assessment meeting occurred either on the date of the informed consent (all within three weeks of the chemotherapy session) or on the date of chemotherapy, depending on patient availability and clinic scheduling. Research staff obtained medical information from each participant’s record or chart (i.e., cancer location, grade, and stage). A biostatistician from the Clinical Investigations Support Office, blinded to study hypotheses, allocated participants to one of three exposures in a 1:1:1 ratio. Exposures included: (1) standard chemotherapy at rest as a control group; (2) a cancer education module as an attention control group; or (3) a mindfulness meditation practice video followed by the cancer education module as the active treatment group. To increase statistical power and to test for group differences by mindfulness exposure, we collapsed groups (1) and (2) (no mindfulness practice) and compared them to group (3) (mindfulness practice). A test of group contrast showed that AUC values did not differ between groups 1 and 2 (p>.05). The original 3-group design aimed to test changes in cancer knowledge, and we categorically refine the groups here to test the exposure of mindfulness practice on salivary cortisol levels. We referred to the videos and protocols in all communications with patients prior to exposures as “educational activities” to limit any expectancy effects.

On the date of chemotherapy, participants were instructed to refrain from taking stimulant medication, smoking, eating, drinking, and brushing their teeth at least 30 minutes prior to their visit to avoid contamination of saliva. All chemotherapy sessions occurred between 10am and 2pm. At the start of chemotherapy, participants provided a baseline saliva sample and subsequent saliva samples at 20 minute intervals for the first 60 minutes of chemotherapy (i.e., baseline and minutes 20, 40, and 60). All intervention exposures were delivered via mobile tablet for purposes of transportability at clinics. At the end of the 60 minute assessment period, participants completed a self-report questionnaire comprised of biobehavioral measures (minutes 60–80). At the close of the questionnaire, participants were thanked by the staff and provided with a $10 gift card to acknowledge their time and effort.

Group Exposures

Participants in the standard care group received routine treatment only as provided at the clinic site. This exposure is best defined as the patient being at rest for 60 minutes while sitting in a chair during chemotherapy. Participants in the cancer education group navigated a 20-minute read-only CRC educational module on a transportable tablet at the start of chemotherapy and then rested for the remaining 40 minutes of chemotherapy. This educational module is available from the Patient Education Institute (X-Plain® Lite) and provides basic information on CRC disease anatomy, etiology, treatment, and prevention on a touch screen. All video modules and study documents were available in both English and Spanish, as preferred by the participant. Participants in the mindfulness practice group engaged in 12-minutes of pre-recorded audio-video instructions on a guided mindful body scan meditation at the start of chemotherapy. The program was developed by author D.S.B. in collaboration with a teacher trained in Mindfulness Based Stress Reduction (MBSR; Lopez Maya) who had over six years of teaching experience. After the mindfulness practice exposure, participants rested for the remaining 8 minutes to reach the 20 minute mark, then completed the 20 minute CRC educational module, then had 20 minutes of rest.

Assessments

Salivary Cortisol

The measurement of cortisol in saliva reliably reflects physiologically active free plasma cortisol levels in blood since unbound plasma cortisol diffuses easily from blood to saliva.³⁷ The collection of saliva is a minimally invasive method for repeated measures of biological specimens,³⁸ thus having high utility with cancer patients in treatment. Research staff timed the four saliva collections, including a baseline collection at the start of chemotherapy and subsequent saliva collections at 20-minute intervals during the first 60 minutes of chemotherapy. Staff provided participants with non-invasive Salivettes (Sarstedt, USA), a commercially available collection device consisting of a dental roll and a centrifuge tube, for the hygienic collection of saliva samples from humans. At the designated collection time, staff asked the participants to remove the cap from the tube, drop the dental roll from the centrifuge tube into their mouth while chewing gently for approximately one minute to allow saturation of the dental roll. Participants then spit the dental roll back into the Salivette tube that was labeled with sample ID numbers and collection time point (0, 20, 40, 60 minutes). We stored Salivette tube specimens at −70°C. At study completion, we sent batched saliva specimens to the Technical University of Dresden (Kirschbaum Laboratory) to be assayed for cortisol quantification via chemiluminescence immunoassay (IBL, Hamburg, Germany). The inter-assay coefficient was <.08 and intra-assay coefficient was <.06 with a lower detection limit of .05 nmol/L.

Biobehavioral Measures

Participants completed a questionnaire inclusive of the following measures that have been psychometrically validated among various populations, including cancer survivors: (1) the Multidimensional Fatigue Symptom Inventory (MFSI) 7-item General Scale designed to assess the principal manifestations of fatigue, with a past week recall period;³⁹ (2) the 21-item Depression, Anxiety, and Stress Scale (DASS) designed to assess a syndrome of distress along three axes, with a past week recall period;⁴⁰ and (3) the Mindfulness Attention Awareness Scale (MAAS) 6-item short version designed to assess mindful and receptive awareness to present moment experience, with a recall period of current everyday experience per measure instructions.^41,42

Statistical Analyses

We report descriptive statistics from Chi-square, t-test, and one-way ANOVA to compare the two exposure groups at baseline on sociodemographic and clinical features. For salivary cortisol in nmol/L, we report area under the curve with respect to increase (AUC_I), area under the curve with respect to ground (AUC_G), and area under the curve above the baseline value (AUC_B) as previously detailed.^43,44 Functioning to simplify the repeated assessment of salivary cortisol while reducing multiple-testing error, AUC represents aggregated data and is derived from a trapezoid formula. Whereas AUC_G pertains to total cortisol output, AUC_I and AUC_AB pertain to the response sensitivity of the HPA axis/cortisol system. We retained negative AUC_I values to avoid omitting information and negative AUC_B values were set to zero. Using AUC_G, AUC_I, and AUC_B as outcomes, simple linear and multiple-linear regression models were estimated and adjusted for age, sex, cancer stage, and time since cancer diagnosis in Stata 14.1 (StataCorp LP, College Station, TX). Square root transformations of AUC were made when necessary to ensure the normality and homoscedasticity of residuals in regression models. Multicollinearity of predictors and auto-correlation were checked for all regression models and no problems were evident. Bivariate correlations were used to test association between AUC_I and biobehavioral measure scores. All hypotheses were tested with a two-sided significance level with α=0.05.

Results

Study entry and sample characteristics

Sixty-five recruits were approached at the clinic sites and signed the informed consent form. Recruits that showed up to their next scheduled chemotherapy appointment (N=57) were officially enrolled in the study and randomly assigned to one group (standard care n=21; cancer education module n= 19; and mindfulness meditation practice video n=17). Combining of the standard care and cancer education groups (no mindfulness) led to n=40. Six participants (n=1 in the mindfulness group and 5 in the no mindfulness group) did not provide sufficient saliva during at least one collection point, making the analytic sample N=51. Table 1 presents description and medical characteristics by exposure group. Scores on all demographic, biological and clinical measures were equivalent across groups at baseline.

Table 1.

Sample characteristics of randomized participants

Variable	Controls	Mindfulness	p
n	40	17
Age	54 (7.8)	54 (9.1)	.54
Sex (female)	20 (50.0)	8 (47.1)	.84
Ethnicity			.41
Hispanic/Latino	12 (30.0)	7 (41.2)
Non-Hispanic	28 (70.0)	10 (58.8)
Primary language			1.0
Spanish	7 (17.5)	3 (17.7)
English	33 (82.5)	14 (82.4)
Education
<9th grade	5 (12.5)	2 (11.8)
High school/GED	10 (25.0)	5 (29.4)
Completed college	18 (45.0)	7 (41.2)
Time since cancer dx			1.0
≤6 months	11 (27.5)	4 (23.5)
>6 months	29 (72.5)	13 (76.5)
Cancer stage
2–3	20 (50.0)	7 (41.2)	.49
4	19 (47.5)	10 (58.8)
Unknown	1 (2.5)	0 (0.0)
MFSI	1.43 (1.02)	1.22 (0.89)	.48
DASS	0.57 (0.53)	0.56 (0.33)	.96
MAAS	5.05 (1.00)	4.93 (1.07)	.70
Cortisol nmol/L
0 minutes	12.22 (5.89)	12.28 (7.48)
20 minutes	11.42 (5.27)	13.77 (7.59)
40 minutes	11.64 (6.25)	13.63 (7.69)
60 minutes	9.55 (5.51)	13.01 (7.88)

Notes. MFSI = Multidimensional Fatigue Symptom Inventory; DASS = Depression, Anxiety, and Stress Scale; MAAS = Mindfulness Attention Awareness Scale

Group exposure effects on cortisol response during chemotherapy

Table 2 shows the results for unadjusted and adjusted models testing the impact of mindfulness exposure on cortisol levels. In unadjusted models, mindfulness exposure versus non-exposure predicted greater aggregated rise in both AUC_I and AUC_B salivary cortisol (AUC_I: β=118.85, p=0.03; AUC_B: β square-root transformed=4.01, p=0.03). Mindfulness exposure versus non-exposure did not significantly predict total cortisol output (AUC_G: β square-root transformed=1.99, p=0.35). After adjusting for biological and clinical covariates, the pattern of results for AUC outcomes remained similar (AUC_I: β=123.21, p=0.03; AUC_B: β square-root transformed=4.15, p=0.03; AUC_G: β square-root transformed=2.02, p=0.34). Figure 1 shows cortisol increases from the time 0 to 20 minutes of chemotherapy. At 20 minutes, 34% (12/35) of participants in the control group showed a cortisol increase as compared to 69% (11/16) of participant in the mindfulness exposure. This difference between the groups was significant (p=.02).

Table 2.

Prediction of salivary cortisol AUC in nmol/L, unadjusted and adjusted estimates

	β	SE	t	p	95% CI
AUCI (respect to increase)
Unadjusted model
Group (Ref.: control)	118.85	52.98	2.24	.03	(12.38, 225.31)
Adjusted modelb
Group (Ref.: control)	123.21	54.33	2.27	.03	(13.72, 232.70)
Age	2.13	3.13	0.68	.50	(−4.18, 8.44)
Female	−17.81	51.03	−0.35	.73	(−120.65, 85.04)
Cancer Stage (Ref.: Stage 2–3)	36.31	51.37	0.71	.48	(−67.22, 139.84)
Time since dx (Ref.: < 6 months)	−80.98	56.01	−1.45	.16	(−129.27, 103.46)
AUCB (respect to baseline)a
Unadjusted model
Group (Ref.: control)	4.01	1.82	2.20	.03	(0.34, 7.68)
Adjusted modelb
Group (Ref.: control)	4.15	1.85	2.24	.03	(0.41, 7.88)
Age	0.03	0.11	0.27	.79	(−0.19, 0.24)
Female	−1.19	1.74	−0.68	.50	(−4.69, 2.32)
Cancer Stage (Ref.: Stage 2–3)	−3.01	1.91	−1.58	.12	(−6.86, 0.83)
Time since dx (Ref.: < 6 months)	2.31	1.75	1.32	.20	(−1.22, 5.84)
AUCG (respect to ground)a
Unadjusted model
Group (Ref.: control)	1.99	2.11	0.94	.35	(−2.25, 6.22)
Adjusted modelb
Group (Ref.: control)	2.02	2.09	0.97	.34	(−2.19, 6.22)
Age	−0.16	0.12	−1.36	.18	(−0.41, 0.08)
Female	−3.07	1.96	−1.56	.13	(−7.01, 0.88)
Cancer Stage (Ref.: Stage 2–3)	1.16	1.97	0.59	.56	(−2.81, 5.14)
Time since dx (Ref.: < 6 months)	−3.07	2.15	−1.43	.16	(−7.41, 1.26)

Notes.

^aSquare-root transformation for AUC;

^bparticipant missing cancer stage data thus reducing analytic sample by one; AUC = area under the curve; Ref = reference group serving as contrast

Figure 1.

Cortisol in nmol/L responders by group exposure. The 20-minute mark is presented due to it having the highest mean cortisol value for any group during the entire assessment period. The timing of this cortisol peak is similar to previously reported trajectories induced by acute stressors.⁵⁰ Representation of all data collection points is shown in the AUC analysis in Table 2.

Correlation of cortisol response and biobehavioral measures

Table 3 shows bivariate correlations between self-reported biobehavioral measure scores and cortisol AUC for the total sample. None of the correlations between cortisol AUC and biobehavioral measure scores reached statistical significance. MAAS was significantly anti-correlated with both MFSI (r=−.46, p<.01) and DAAS (r=−.54, p<.01) while MFSI was significantly correlated with DASS (r=−.49, p<.01). All of these significant biobehavioral correlation coefficients were in the range of a large effect size.

Table 3.

Bivariate correlations between cortisol in nmol/L and biobehavioral measure scores

Variable	AUCI	AUCB	AUCG	MFSI	DAAS	MAAS
AUCI	1
AUCB	.83*	1
AUCG	.16	.42*	1
MFSI	−.07	−.10	−.11	1
DASS	.08	.01	.03	.49*	1
MAAS	.09	.07	.11	−.46*	−.54*	1

Notes

^*p<.001; AUC = area under the curve; MFSI = Multidimensional Fatigue Symptom Inventory; DASS = Depression, Anxiety, and Stress Scale; MAAS = Mindfulness Attention Awareness Scale

Discussion

To better understand the clinical relevance of mind-body practice delivered during chemotherapy, this randomized, controlled experiment exposed colorectal cancer patients to mindfulness in the form of the body scan and assessed salivary cortisol profiles during the first 60 minutes of chemotherapy. Results show the mindfulness exposure group relative to the control group yielded significantly greater acute salivary cortisol reactivity during chemotherapy infusion. Findings were evident for two AUC approaches (i.e., AUC_I and AUC_B) as well as after adjusting for important biological and clinical measures, including age, sex, cancer stage and time since diagnosis. More than twice as many patients in the mindfulness group as compared to controls displayed a cortisol rise from baseline to 20 minutes (69% vs. 34%). These findings suggest that mindfulness practice during chemotherapy infusion may awaken cortisol reactivity as a counter to detrimental HPA axis blunting that is previously observed in cancer survivors and patients and survivors.

Our findings add to the knowledge garnered from previous studies that have examined cancer-related HPA axis dysregulation. Specifically, previous results indicate the occurrence of cortisol blunting in terms of acute reactivity and diurnal rhythm in cancer patients as well as in cancer survivors.^17,18 Our findings are specifically pertinent to a previous study that showed acute cortisol blunting in response to a recommended medical procedure (mammography) among cancer survivors.¹⁹ Considering that such blunting might be caused by repeated physiological and psychological efforts to cope with demand, it appears that mindfulness practice might offer a unique mechanistic route to activate acute cortisol reactivity during the prescribed medical treatment of chemotherapy, which can be a stressful event for patients. Our findings suggest that blunting of acute cortisol reactivity during cancer treatment is malleable to psychobehavioral intervention, denoting an opportunity for new advances in integrative oncology specific to mind-body interventions provided to patients during chemotherapy.

Although research on the effects of mindfulness practice on cortisol profiles is scant at present,³⁰ initial work shows that cancer patients exposed to a mindfulness intervention are protected from the diurnal cortisol blunting observed in controls.³¹ Interestingly, the mindfulness group in the Carlson study reported corresponding and relative reductions in stress symptoms. A quasi-experimental study also showed mindfulness intervention exposure to be associated with profiles that suggested significantly less diurnal cortisol blunting. Again, this change was significantly associated with improved overall global quality of life.³² Our findings uniquely add to this work by showing mindfulness exposure can also awaken cortisol reactivity as a counter to neuroendocrine blunting during chemotherapy infusion. As such, this study provides initial evidence and methodological framework for investigating the effect of mindfulness on acute cortisol reactivity during routine medical treatment for cancer.

Little is known about the mechanistic processes underlying how mindfulness impacts a blunted cortisol profile; however, content reviews are just beginning to uncover the biological significance of mindfulness practice and its function on disease processes (see review⁴⁵). As an initial exploration of the topic, we suggest that mindfulness practice represents a novel learning experience founded on stress arousal reduction – a process that engages attention and awareness to bodily sensations and experiences without judgment or reactivity.²¹ This lends directly to the HPA axis involvement in novel learning exposures and states of eustress that are linked with positive rather than negative outcomes.^33–36 Thus, mindfulness exposure might exact a demand to recruit attentional resources and learning faculties in a manner that is detectable via acute cortisol reactivity yet does not translate physiologically to making the patient experience the demand as a stressful or negative event. This notion was partially supported by our finding of equal distress levels reported at the conclusion of chemotherapy across groups.

Results did not lend support for our exploratory aim, which was to test for significant associations between cortisol reactivity levels and self-report of biobehavioral factors (i.e., distress, fatigue, and mindfulness). Here it is important to note that the interpretation of our results is limited by our smaller sample size and the past-week recall period for fatigue and distress. However, we did find that mindfulness scores reported on the same day as chemotherapy for the full sample were significantly anti-correlated with fatigue and distress scores with a large bivariate effect size, which does corroborate findings in the previous literature among colorectal cancer patients.⁴⁶ These correlations also lend possible support for future use of mindfulness practice to bolster mindfulness skills to support a reduction in fatigue and distress in cancer patients during the course of their chemotherapy treatments. Such intervention efforts have generally proven beneficial for cancer survivors and lend biologically relevant changes in immune function,^24,47–49 yet little is known about effects on cancer patients during their clinical treatment.

Strengths of our study include it being the first experiment we know of to examine the effect of mindfulness exposure on cancer-relevant physiological markers during chemotherapy infusion. We enrolled colorectal cancer patients, a significant proportion being Hispanic/Latino, from two oncology clinics that are all features that further the generalizability of our findings. The repeated measurement of cortisol and use of validated biobehavioral self-report measures lend to future replication of this study. Further the use of a pre-recorded video and its delivery on a transportable tablet allowed for exposure standardization across participants and lends to future integration of the protocol into routine oncology care. Given that a video intervention is readily available and transportable, dissemination efforts have translational value for clinical oncology. The use of the body scan as the mindfulness practice is a straightforward and solid model for novices unfamiliar with mindfulness. Limitations of the study include a smaller sample size and lack of biobehavioral measurements prior to chemotherapy due to time constraints. We referred to all study activities and protocols as “educational activities” to support masking of exposures, yet historical and expectancy biases are possible for those with previous meditation experience. It is possible that the body scan induced relaxation, thus future experiments may benefit from offering different mindfulness exposures (e.g., breath awareness, open monitoring awareness) and comparing them with relaxation-focused exposures to better determine if mindful awareness or relaxation is the mechanism of action. The mindfulness exposure was 32 minutes while the education exposure was 20 minutes, making exposure time a possible explanation for some of the change observed in cortisol, thus warranting future research to match the time of exposures across all conditions. Moreover, future studies will benefit from repeated measurement of self-report variables during chemotherapy that align with saliva collection to determine if chemotherapy induces changes in state-like distress, fatigue, and other biobehavioral measures.

To conclude, our findings show that mindfulness practice may awaken acute cortisol reactivity as a counter to HPA axis blunting that is often observed in cancer patients, specifically during chemotherapy infusion. The longer-term impact of this awakening remains unknown, yet it is understood that cortisol blunting in cancer patients is predictive of adverse health outcomes and reduced survival. Pending future replication and advancement of these findings, patient engagement in mindfulness practice appears to be relevant to cancer-related physiology during chemotherapy, which might have implications for treatment response and longer-term cancer survivorship outcomes.

Condensed Abstract.

Cortisol blunting in cancer patients is predictive of adverse health outcomes and reduced survival. Our findings show that mindfulness practice may increase acute cortisol reactivity as a counter to cortisol blunting that is often observed in cancer patients, specifically during chemotherapy infusion.