Symptom management with massage and acupuncture in post-operative cancer patients: A Randomized Controlled Study Wolf Mehling & Bradly Jacobs (PIs) Michael Acree, Leslie Wilson , Alan Bostrom, Jeremy West, Joseph Acquah, Beverly Burns, Jnani Chapman, Frederick Hecht University of California San Francisco Funding by Mount Zion Health Fund

Background Prior studies of acupuncture support its use for post-operative pain, vomiting, and anxiety . Prior uncontrolled studies of massage support its use for symptom management (pain, anxiety) in cancer patients. No studies of combined acupuncture and massage for symptom management following cancer surgery.

Background Anecdotal benefits from existing Perioperative Integrative Medicine Service (PIMS) at Mount Zion Cancer Center, UCSF. Acupuncture and massage offered to in- and outpatients at major Cancer Centers in the US

Purpose of this study: to obtain pilot data on the effectiveness of an inpatient perioperative integrative medicine service (PIMS): post-operative acupuncture and massage for hospitalized cancer patients.

Methods Subjects: Adult inpatients hospitalized for at least 3 days for cancer-related surgeries  breast cancer surgery: mastectomy or reconstructive surgery;  abdominal surgery for intestinal or hepatic malignancies;  pelvic surgery for ovarian, uterine, or cervical malignancies;  urological surgery for testicular, prostate, bladder, or renal malignancies;  head and neck cancer surgery Recruitment: pre-operative Prepare Clinic Site: UCSF Mount Zion Hospital.

Methods Randomization: 2:1 after baseline assessment on POD1 Intervention: • PIMS: massage and acupuncture on POD 1 + 2 versus • usual care alone. Surgery Day POD1 POD2 POD3 Q M&A Q M&A Q Q

Methods Primary outcome: pain severity (NRS 0-10) measured 4 times from baseline on POD1 to POD 3. Secondary outcomes: • nausea severity [range 0-10], • number of vomiting episodes, • tension/anxiety and depression (POMS subscales, range 1-5), • health care utilization. Analyses: intention-to-treat by mixed-effect regression analyses for repeated measures controlling for baseline values and potential confounders, t-tests, and Fischer exact.

Results 174 eligible patients 24 declined (14%) 180 consecutive patients approached 6 not eligible (2 diagnosis, 4 language) 174 eligible patients 24 declined (14%) 150 enrolled prior to hospital admission 12 rescheduled, declined after surgery 138 randomized after surgery on POD 1 93 PIMS 45 control

Results n=93 PIMS (massage and acupuncture) group 87 (94%) received  1 massage 70 (75%) received 2 massages 58 (62%) received  1 session of acupuncture 33 (36%) received 2 sessions of acupuncture 4 (4%) did not receive any intervention

Baseline Characteristics PIMS n=93 Control n=45 P Age 56 ± 2 59 ± 2 0.23 Sex (female) 52% 44% 0.62 Ethnicity (white) 69% 78% 0.51 Education (college) 61% 53% 0.08 Pain at BL 3.5 ±2.2 3.1 ±2.4 0.33 Depressed at BL 1.7 ±0.8 1.4 ±0.4 0.01 Anxiety at BL 2.1 ±0.9 1.8 ±0.9 0.12 ± standard deviation

Baseline Characteristics PIMS Control P n=93 n=45 type of cancer Abdom./pelvic 23 (25%) 7 (16%) prostate/testic. 16 (18%) 14 (31%) bladder/kidney 19 (21%) 11 (24%) breast 18 (20%) 7 (16%) surgery narcotics pre-op 15% 14% 0.83 epidural 31% 25% 0.61 hours anesthesia 5.4 ±1.7 4.5 ±2.2 0.22 hours procedure 3.8 ±1.8 4.1 ±2.4 0.47 0.30

Pain Scores in 138 Patients PIMS n=93 Control n=45 Pain since surgery 3.5 ± 2.2 3.1 ± 2.4 Pain after intervention POD1 2.5 ± 2.1 3.1 ± 2.3 Pain after intervention POD2 2.2 ± 1.9 2.9 ± 2.4 Pain on POD3 2.1 ± 1.8 2.7 ± 2.0 Change in Pain from baseline* -1.4 ± 2.2 -0.6 ± 2.3 * mixed-effects regression analysis controlled for education, baseline pain and depression: p = 0.038 (intention-to-treat analysis)

Pain Scores in 90 Patients with Pain 3 at Baseline PIMS n=62 Control n=28 Pain since surgery 4.3 ± 2.0 3.6 ± 2.1 Pain after intervention POD1 3.0 ± 2.2 3.6 ± 2.3 Pain after intervention POD2 2.2 ± 1.8 3.8 ± 3.3 Pain on POD3 2.5 ± 1.9 3.3 ± 1.9 Change in Pain from baseline* -1.8 ± 2.3 -0.3 ± 2.3 * mixed-effects regression analysis controlled for education, baseline pain and depression: p = 0.001 (post-hoc intention-to-treat analysis)

Mean Pain Scores (90 patients with 3/10 pain) PIMS usual care 5 graphs to table 2 4.5 4 3.5 3 2.5 2 1.5 1 .5 POD 1 pre POD 1 post POD 2 POD 3 p = 0.001 mixed-effects regression for repeated measures (controlled for education, baseline pain and depression)

Secondary Outcomes in 131 patients (88 PIMS; 43 control) ¹Range 0-10; ²Range 1-5 *mixed-effects regression analyses controlled for education, depression and outcome at baseline intention-to-treat analyses

Conclusions Massage and acupuncture had a high acceptance rate (86%) in hospitalized cancer patients. Compared with usual care alone, the combination of massage and acupuncture was associated with • reduced post-operative pain and • reduced depression, in hospitalized cancer patients. The next step should be a larger clinical trial to assess this intervention compared with attention controls.

In press: Journal for Pain and Symptom Management Thank You

Acupuncture and Nausea / Vomiting 22 patients with any nausea at baseline improved by 4.52.9 if they received acupuncture (10), and by 2.42.5 if they did not receive acupuncture (12) (p=0.038*). 28 patients with any vomiting at baseline improved by 2.0 3.3 if they received acupuncture (14) and by 1.6 4.6 if they did not receive acupuncture (14) (p=0.035*) * controlled for baseline depression (post-hoc as-performed repeated measures analyses).

Mean Change Scores for Pain by Diagnostic Subgroups for Patients with 3/10 Pain at Baseline (n = 86) type of cancer (n) PIMS (n) control (n) P* ES abdom./pelvic (21) -2.3 ±2.2 (16) +0.2 ±3.6 (5) .13 .98 prostate/testic. (14) -1.9 ±1.5 (9) - 0.2 ±2.2 (5) .03 .98 bladder/kidney (19) -2.1 ±1.8 (11) - 2.3 ±2.0 (8) .86 -.10 breast (17) -1.9 ±1.8 (14) - 0.3 ±0.6 (3) .14 .66 others (15) -2.6 ±1.8 (10) - 2.4 ±3.0 (5) .30 .09 *P-values by mixed-effects regression analyses for repeated measures from baseline POD1 to POD3 controlled for education, baseline pain and depression for complete subgroups irrespective of baseline symptom scores (all 138 patients)