Phase 1/2 Randomized Clinical Trial of In-clinic acupuncture Prior to Bacillus Calmette-Guérin in Patients with High-risk Non-muscle-invasive Bladder Cancer.

BACKGROUND: Treatment-related dose-limiting dysuria and irritative bladder symptoms are common in patients receiving intravesical bacillus Calmette-Guérin (BCG) to treat non-muscle-invasive bladder cancer (NMIBC). Acupuncture has been shown to reduce pain and urinary urgency/frequency in other patient populations. OBJECTIVE: To evaluate the feasibility, safety, and tolerability of weekly in-clinic preprocedural acupuncture among patients receiving induction BCG. DESIGN, SETTING, AND PARTICIPANTS: Patients with high-risk NMIBC undergoing induction BCG were randomized 2:1 to a standardized acupuncture protocol (acupuncture) versus the standard-of-care control arm. INTERVENTION: In-office acupuncture prior to each BCG instillation. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES: Feasibility was assessed via recruitment, retention, and intervention adherence. Acupuncture safety and tolerability were assessed via physician-reported Common Terminology Criteria for Adverse Events version 5.0 and adverse events (AEs). Secondary endpoints included BCG treatment adherence, patient-reported BCG-related toxicity, and bladder cancer-specific and generic (European Organisation for Research and Treatment of Cancer [EORTC]-QLQ-NMIBC-24 and EORTC-QLQ-NMIBC-C30) quality of life (QOL). Subjective assessments of acupuncture acceptability were performed through patient surveys. RESULTS AND LIMITATIONS: A total of 43 individuals were randomized 2:1 to the acupuncture (n = 28) versus control (n = 15) group. The median age was 70.3 yr, and 76% were male. Week 7 follow-up surveys were completed by 93%; six participants withdrew early due to disease progression, refractory gross hematuria, or preference. Acupuncture was delivered successfully prior to each BCG treatment, with no acupuncture-related AEs or interruptions to induction BCG. BCG-attributed AEs were reported by 91% acupuncture and 100% control individuals, including pain (28% vs 43%, p = 0.34) and urinary symptoms (62% vs 79%, p = 0.31). Comparing acupuncture patients with controls, change in QOL over the study period demonstrated greater improvements in median urinary symptoms (9.5, interquartile range [IQR] 0.0-19.0 vs 0.0, IQR -14.3 to 7.1; p = 0.02) among patients in the acupuncture arm. Of the acupuncture patients, 96% reported that acupuncture was "very/extremely helpful," and 91% would recommend acupuncture to other patients. Limitations include modest sample size and single-institution design. CONCLUSIONS: Acupuncture prior to induction BCG treatments is feasible and safe. In this phase 1/2 trial, improved urinary function scores were observed among patients undergoing acupuncture. Patients receiving acupuncture reported high degrees of satisfaction with treatments. PATIENT SUMMARY: We evaluated the safety and feasibility of delivering acupuncture in a urology clinic prior to weekly intravesical bladder cancer treatments with bacillus Calmette-Guérin (BCG) in a randomized controlled trial. We found that acupuncture could be delivered safely prior to weekly BCG instillations and that the use of acupuncture was associated with high patient satisfaction and a decrease in patient-reported urinary symptoms compared with usual care.

Characteristics and Challenges of Providing Acupuncture and Chinese Herbal Medicine in Oncology Treatment: Report of Survey Data and Experience of Five Unique Clinical Settings.

Acupuncture is an integrative therapy with strong evidence to support its use in the oncology setting, yet barriers exist for implementation into conventional medical clinics. Though acupuncture is recommended in clinical practice guidelines for oncology, there is little data in the literature showing how acupuncture and other related therapies, including herbal medicine are successfully implemented in some oncology clinics, while others experience barriers to care. To characterize the current use of acupuncture (ACU) and herbal medicine (HM) in oncology clinics, we collected general demographic and usage data from 5 example clinics. In addition, to better understand the barriers faced by ACU and HM clinics in implementing acupuncture as a treatment modality, a survey was deployed to 2320 members of the Society for Integrative Oncology. This article examines the characteristics of oncology settings around the world, and shares data from the survey on the use of these therapies in the field of oncology. The primary barrier to acupuncture care, as reported by providers, was cost. With just under 70% of the oncologists reporting it as the most important obstacle. Additional barriers to implementation included concerns about competency and training, accessibility and safety of herbal medicine during treatment. Though acupuncture is being incorporated into more conventional oncology settings, organized strategies for implementation involving payers and policymakers is needed.

Use of acupuncture with acupressure in addition to standard-of-care cryotherapy to decrease chemotherapy-associated neuropathy in patients with gastrointestinal malignancies receiving oxaliplatin-based chemotherapy: Study protocol for a randomized, controlled pilot and feasibility study.

BACKGROUND: Oxaliplatin is a key chemotherapeutic agent in the treatment of local and metastatic gastrointestinal (GI) malignancies. Dose density and treatment adherence can be limited by chemotherapy-induced peripheral neuropathy (CIPN). Early research suggests CIPN incidence and severity may be mitigated by acupuncture, but rigorous data in GI oncology patients is limited. Here, we describe the protocol of a randomized, waitlist-controlled pilot study testing the use of preemptive of acupuncture plus acupressure to decrease CIPN and chemotherapy-related toxicities. METHODS: Patients with a GI malignancy (n = 56) with planned 5-fluorouracil (5-FU) and oxaliplatin IV (FOLFOX, FOLFIRINOX) every 2 weeks are being recruited. Additional concurrent anti-neoplastic agents may be used. Enrolled patients are randomized 1:1 to a 3-month intervention of Arm A: acupuncture with acupressure and standard-of-care treatment, or Arm B: standard-of-care alone. In Arm A, on days 1 and 3 of each chemotherapy cycle a standardized acupuncture protocol is administered and patients are taught self-acupressure to perform daily between chemotherapy treatments. Patients in both arms are given standard-of-care oral and peripheral (hands/feet) ice chip cryotherapy during oxaliplatin administration. CIPN and other symptoms are assessed at baseline, 6 weeks, and 3 months from registration. The primary endpoint is CIPN severity at 3 months (EORTC-CIPN 20). Additional endpoints evaluate CIPN incidence (CTCAE, Neuropen, tuning fork); incidence of pain, fatigue, nausea, oral dysesthesia, and anxiety; and feasibility (recruitment, retention, adherence, acceptability). If warranted, trial results will inform the design of a multi-center trial to expand testing of the intervention to a larger patient cohort.

Effects of acupuncture to decrease adverse events in patients with high-risk non-muscle invasive bladder cancer receiving induction intravesical BCG therapy: Study protocol for a randomized, controlled pilot and feasibility study.

Background: Treatment-related serious adverse events (SAEs) are common in patients receiving intravesical Bacillus Calmette-Guerin (BCG) for the treatment of high-risk nonmuscle-invasive bladder cancer (NMIBC). Here we describe the protocol of a randomized, attention/waitlist-controlled feasibility pilot study testing the use of acupuncture to decrease SAEs and treatment interruptions in this population. The primary objectives are to evaluate the feasibility and efficacy of conducting pre-procedure acupuncture in a Urology Clinic. Methods: A total of 45 patients will be recruited and randomized in a 2:1 ratio (treatment arm: attention/waitlist control). Eligibility criteria include 1) age 18 years or older, 2) English-speaking, 3) high-risk NMIBC, 4) no acupuncture in the previous 3 months, and 5) willing and able to participate in trial activities. Patients in the treatment arm will receive acupuncture prior to weekly BCG for a total of six weeks. Methods were developed to train and monitor research acupuncturists and included online and in-person training, study manuals, and monthly meetings throughout the study period. Feasibility assessments include evaluation of the recruitment, retention and protocol adherence to acupuncture treatment, and measurement of CTCAE v5.0 adverse events specific to acupuncture, and clinic staff surveys regarding the intervention impact on clinic workflow. Efficacy measures will be compared between treatment and control groups including: EORTC-QLQ-NMIBC-24, EORTC-QLQ-C30, CTCAE v5.0, medication journal, healthcare utilization, current use of complementary, alternative, and integrative therapies, and acupuncture expectancy and treatment preference. Trial results will inform the design of a multi-center trial to expand testing of the protocol to a larger patient cohort.

Micropulse Cyclophotocoagulation: A Multicenter Study of Efficacy, Safety, and Factors Associated With Increased Risk of Complications.

PRéCIS:: Micropulse cyclophotocoagulation (MPCP) lowered intraocular pressure (IOP) in the short-term but nearly half required additional intervention. Mydriasis was the most common complication (11%); 15% lost ≥3 Snellen lines of acuity; 11% had persistent complications at last follow-up. PURPOSE: The purpose of this study was to evaluate the efficacy and complications of MPCP in a large series of patients with all stages of glaucoma. DESIGN: Multicenter, retrospective chart review of patients from 3 clinical sites. PARTICIPANTS: One hundred sixty-seven eyes of 143 patients. METHODS: MPCP was performed with 2000 mW energy, 31.3% duty cycle and 2 to 4 180-degree applications of 80 seconds duration each per treatment. The procedure was considered a failure if any of the following occurred: additional IOP lowering intervention, <20% IOP reduction from baseline at the last follow-up (with or without medication), or severe complications. RESULTS: Mean age was 71 years, 53% were female, and 53% were Asian. 60% of eyes had POAG, 63% were pseudophakic, 38% had prior glaucoma surgery, and 51% had Snellen visual acuity (VA) of 20/40 or better. Mean follow-up time was 11.9±7.8 months. Mean IOP was 21.9±8.4 mm Hg before intervention, and 17.4±7.2 mm Hg at last follow-up (P<0.0001). There was no change in mean logMAR VA (P=0.0565) but 15% lost ≥3 Snellen lines of VA. The success rate was 36.5% (61/167 eyes) at last follow-up. The probability of survival by Kaplan-Meier analysis was 82%, 71%, and 57% at 3, 6, and 12 months after the procedure, respectively. The reasons for failure were additional intervention in 47%, inadequate IOP reduction in 14%, and severe complication in 1.8%. In a multivariable Cox proportional hazard model, female sex was associated with a 56% decrease in failure rate compared with males (P<0.0001), while a unit increase in baseline IOP corresponded with a 5.7% increase in failure rate (P<0.0001). If repeat MPCP was allowed then success rate increased to 58%. There were no complications in 73% (122/167) but 11% (18/167) had persistent complications at the last follow-up and half of these 18 eyes had decrease in VA of 1 to 6 Snellen lines. Asian race (odds ratio 13.5, P=0.0131) and phakic status (odds ratio 3.1, P=0.0386) were associated with higher odds of developing mydriasis, which was the most common complication. CONCLUSIONS: MPCP lowered IOP in the short-term but nearly half required additional IOP lowering intervention. Potential complications should be discussed in detail especially when the procedure is being considered for those with good VA and early stage disease.

Reduction of Opioid Use by Acupuncture in Patients Undergoing Hematopoietic Stem Cell Transplantation: Secondary Analysis of a Randomized, Sham-Controlled Trial.

OBJECTIVE: To evaluate acupuncture as a nonpharmacologic intervention for pain management in patients undergoing hematopoietic stem cell transplantation (HSCT). METHODS: Adult patients with multiple myeloma undergoing high-dose melphalan chemotherapy and autologous peripheral blood HSCT were randomized to receive either true (TA) or sham acupuncture (SA) once daily for five days starting on the day after chemotherapy. Use of pain medications and pain scores were assessed at baseline and at days 5, 15, and 30 after transplantation. RESULTS: Among 60 evaluable subjects, the SA group (vs TA) had greater than five times odds of increasing pain medication use from baseline. Among patients who were opioid nonusers at baseline, all 15 patients in the TA group remained free from opioid use at the end of the study. In contrast, 20% of those in the SA group (four of the 20 patients) started to use opioids after chemotherapy and stem cell infusion (day 5) and 40% (eight of the 20) had become opioid users by day 30 after HSCT (Fisher exact test P = 0.006). Among patients who were taking opioids at baseline, 14% in the TA group vs 10% in the SA group increased opioid intake at day 5, and 21% (TA) vs 30% (SA) at day 30 (P = 0.86). CONCLUSIONS: Acupuncture appears to significantly reduce the need for pain medications during HSCT and the number of post-HSCT opioid users among baseline opioid nonusers. It warrants further studies as an opioid-sparing intervention for pain in HSCT patients.

Acupuncture for reduction of symptom burden in multiple myeloma patients undergoing autologous hematopoietic stem cell transplantation: a randomized sham-controlled trial.

PURPOSE: Hematopoietic stem cell transplantation (HCT) is potentially curative for a number of hematologic malignancies, but is associated with high symptom burden. We conducted a randomized sham-controlled trial (RCT) to evaluate efficacy and safety of acupuncture as an integrative treatment for managing common symptoms during HCT. METHODS: Adult patients with multiple myeloma undergoing high-dose melphalan followed by autologous HCT (AHCT) were randomized to receive either true or sham acupuncture once daily for 5 days starting the day after chemotherapy. Patients and clinical evaluators, but not acupuncturists, were blinded to group assignment. Symptom burden, the primary outcome was assessed with the MD Anderson Symptom Inventory (MDASI) at baseline, during transplantation, and at 15 and 30 days post transplantation. RESULTS: Among 60 participants, true acupuncture produced nonsignificant reductions in overall MDASI core symptom scores and symptom interference scores during transplantation (P = .4 and .3, respectively), at 15 days (P = .10 and .3), and at 30 days posttransplantation (P = .2 and .4) relative to sham. However, true acupuncture was significantly more efficacious in reducing nausea, lack of appetite, and drowsiness at 15 days (P = .042, .025, and .010, respectively). Patients receiving sham acupuncture were more likely to increase pain medication use posttransplantation (odds ratio 5.31, P = .017). CONCLUSIONS: Acupuncture was well tolerated with few attributable adverse events. True acupuncture may prevent escalation of symptoms including nausea, lack of appetite, and drowsiness experienced by patients undergoing AHCT, and reduce the use of pain medications. These findings need to be confirmed in a future definitive study. TRIAL REGISTRATION: NCT01811862.