Susan Q. Li

Do attitudes and beliefs regarding complementary and alternative medicine impact its use among patients with cancer? A cross‐sectional survey

Complementary and alternative medicine (CAM) incorporates treatments used by cancer survivors in an attempt to improve their quality of life. Although population studies have identified factors associated with its use, to the best of the authors knowledge, assessment of why patients use CAM or the barriers against its use have not been examined to date.

Expectancy in Real and Sham Electroacupuncture: Does Believing Make It So?

BACKGROUND The large placebo effect observed in prior acupuncture trials presents a substantial challenge for interpretation of the efficacy of acupuncture. We sought to evaluate the relationship between response expectancy, a key component of the placebo effect over time, and treatment outcome in real and sham electroacupuncture (EA). METHODS We analyzed data from a randomized controlled trial of EA and sham acupuncture (SA) for joint pain attributable to aromatase inhibitors among women with breast cancer. Responders were identified using the Patient Global Impression of Change instrument at Week 8 (end of intervention). The Acupuncture Expectancy Scale (AES) was used to measure expectancy four times during the trial. Linear mixed-effects models were used to evaluate the association between expectancy and treatment response. RESULTS In the wait list control group, AES remained unchanged over treatment. In the SA group, Baseline AES was significantly higher in responders than nonresponders (15.5 vs 12.1, P = .005) and AES did not change over time. In the EA group, Baseline AES scores did not differ between responders and nonresponders (14.8 vs 15.3, P = .64); however, AES increased in responders compared with nonresponders over time (P = .004 for responder and time interaction term) with significant difference at the end of trial for responders versus nonresponders (16.2 vs 11.7, P = .004). CONCLUSIONS Baseline higher response expectancy predicts treatment response in SA, but not in EA. Divergent mechanisms may exist for how SA and EA influence pain outcomes, and patients with low expectancy may do better with EA than SA.

Acupuncture for Dyspnea in Lung Cancer Results of a Feasibility Trial

Purpose. Dyspnea is a common and distressing symptom for patients with lung cancer (LC) because of disease burden, therapy toxicity, and comorbid illnesses. Acupuncture is a centuries-old therapy with biological plausibility for relief of dyspnea in this setting. This pilot study aimed to evaluate the feasibility and preliminary effectiveness of acupuncture for dyspnea among patients with LC. Methods. Eligible patients had a diagnosis of LC and clinically significant dyspnea without a clear organic cause. The treatment consisted of 10 weekly acupuncture sessions, with a follow-up visit 4 weeks after therapy. The primary outcome was dyspnea severity as measured using a validated Numerical Rating Scale (NRS) of 0 to 10 (10 being “most severe shortness of breath imaginable”). Results. We enrolled 12 patients in the study. The median age was 64.5 years; 66.7% of the patients were female, and 66.7% were Caucasians. Among those enrolled, 10 (83.3%) were able to complete all 10 acupuncture sessions. Acupuncture was well tolerated; adverse events were mild and self-limited. Mean (SD) dyspnea scores on the NRS improved from 6.3 (1.7) at baseline to 3.6 (1.9; P = .003) at the end of treatment and 3.2 (2.3; P = .008) at follow-up. Fatigue and quality of life also improved significantly with acupuncture (P < .05). Conclusion. Among patients with LC, acupuncture was well tolerated and exhibited promising preliminary beneficial effects in the treatment of dyspnea, fatigue, and quality of life. Performing a trial in this population appears feasible.

Abstract P5-01-06: 18F-radiolabeled PARP-1 inhibitor uptake as a marker of PARP-1 activity in breast cancer

Objectives: The nuclear enzyme PARP-1 plays a central role in sensing DNA damage and facilitating repair. Tumors with BRCA1/2 mutations are highly dependent on PARP-1 as an alternative mechanism for DNA repair, and PARP inhibitors generate synthetic lethality in tumors with BRCA mutations, resulting in cell cycle arrest and apoptosis. Zhou et al. recently synthesized an 18 F-labeled PARP-1 inhibitor ( 18 F-FluorThanatrace) for PET, and demonstrated high specific tracer uptake in a xenograft model of breast cancer (Zhou, Bioorg Med Chem, 22:1700, 2014). The current study seeks to quantify the relationship between 18 F-FluorThanatrace binding (both in vitro and on PET imaging of human tumor xenografts) and the level of constitutively active PARP-1, using multiple human breast cancer cell lines, including a BRCA1 defective line. Methods: BRCA1 defective HCC1937, triple negative MDA-MB-231, and luminal A MCF-7 human breast cancer lines were assessed for constitutive PARP-1 activity via a chemiluminescent ELISA assay for PAR and by Western blot. The same cell lines were incubated with 18 F-FluorThanatrace over various time increments, and tracer uptake was assayed via a gamma counter. Specificity of tracer binding was verified via co-incubation with competitive inhibitor Olaparib, and specific tracer uptake was calculated as the difference between uptake with and without Olaparib. Specific tracer uptake was compared to levels of constitutive PARP-1 activity in all cell lines. In addition, HCC1937 and MDA-MB-231 xenograft tumor models were imaged via 18 F-FluorThanatrace-PET/CT, and PET uptake was correlated with PARP-1 activity. Results: BRCA1-defective HCC1937 had higher constitutive PARP-1 activity than cell lines with intact BRCA1. In vitro levels of 18 F-FluorThanatrace uptake correlated with constitutive PARP-1 activity across cell lines. In addition, 18 F-FluorThanatrace measured by PET in xenograft breast cancer tumor models correlated with constitutive PARP-1 activity. Conclusions: Tumor uptake of 18 F-FluorThanatrace, both in vitro and on PET imaging of xenograft tumor models, quantitatively reflects differences in PARP-1 activity across different breast cancer cell lines, including BRCA1 defective. This motivates further studies of 18 F-FluorThanatrace as an in vivo measure of PARP-1 activity and possibly as a predictive marker for PARP-1 therapy in patients, including those with BRCA1/2 mutations. Citation Format: Edmonds CE, Lieberman BP, Xu K, Zeng C, Makvandi M, Li S, Hou C, Lee H, Greenberg RA, Mankoff DA, Mach RH. 18 F-radiolabeled PARP-1 inhibitor uptake as a marker of PARP-1 activity in breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-01-06.

Abstract PD4-7: A randomized placebo-controlled trial of acupuncture and gabapentin for hot flashes among breast cancer survivors

Purpose Hot flashes are a common and debilitating symptom negatively affecting the quality of life of breast cancer survivors. We sought to compare the short and long term effects of electro-acupuncture (EA) vs. gabapentin for hot flashes among breast cancer survivors. Patients and Methods We conducted a randomized controlled trial of EA vs. gabapentin vs. placebos (sham acupuncture [SA] or placebo medication) in women with breast cancer who had completed primary cancer treatments and experienced bothersome hot flashes twice daily or greater. Acupuncturists performed ten EA/SA treatments over eight weeks using a manualized protocol with 2 Hz electro-stimulation delivered by a TENS unit. Acupuncturists administered SA using Streitberger (non-penetrating) needles at non-traditional acupuncture points without electro-stimulation. Gabapentin (900 mg daily) or placebo medication were continued for eight weeks and then weaned off. The primary endpoint was the hot flash composite score measured by the daily diary at the end of the intervention (Week 8). A secondary endpoint, durability of response, was evaluated at Week 24 from randomization. Longitudinal mixed effects models were used to evaluate change in outcomes over time and group differences. Results Of 120 randomly assigned patients, the mean age was 52.3, 75% were White, 12.5% were peri-menopausal, and 20%/25%/37.5% had natural/surgically/chemically induced menopause, respectively. By Week 8, significant group differences were observed. Mean reduction in hot flash composite scores was greatest in the EA group, followed by SA and gabapentin, with placebo medication having the lowest reduction in hot flashes (-7.4 vs. –5.9 vs. –5.2 vs. –3.4, p=0.0003). By Week 24 and off treatment, reduction in hot flashes in the EA group persisted whereas the hot flashes in the gabapentin group retuned to baseline. The reduction in hot flashes was greatest in the EA group, followed by SA, placebo medication, and gabapentin (-8.5 vs. –6.1 vs. –4.6 vs. –2.8, p=0.0024). No serious adverse events were reported in any groups. The gabapentin group had the highest percentage of participants reporting treatment- related adverse events followed by placebo medication, EA, and SA (48.4% vs. 29.0% vs. 19.3% vs. 3.2%, p=0.004). Conclusion: Electro-acupuncture was more effective than gabapentin, sham acupuncture, or placebo medication in reducing hot flashes for breast cancer survivors both short term and long term with few side effects. Gabapentin produced significant short term reduction in hot flashes that did not persist off medication and was associated with more side effects. Clinical Trial Registration: NCT01005108. Citation Format: Jun J Mao, Sharon X Xie, Marjorie A Bowman, Deborah Bruner, Susan Q Li, Angela DeMichele, John T Farrar. A randomized placebo-controlled trial of acupuncture and gabapentin for hot flashes among breast cancer survivors [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr PD4-7.

P04.86. Socio-demographic variations in barriers to participation in an acupuncture clinical trial.

Purpose As breast cancer survivors (BCS) increasingly use complementary and alternative medicine, randomized controlled trials (RCT) are needed to assess the safety and efficacy of these therapies to guide appropriate clinical use. However, many RCTs face poor patient accrual, especially among populations at risk for health disparities. The purpose of this study is to quantify the barriers to participation in an acupuncture clinical trial among BCS, and to identify the socio-demographic factors associated with these barriers.