Integrative oncology: The value of acupuncture in cancer treatment

1. Integrative oncology: The value of acupuncture in cancer treatment Cesar Rodriguez Valdes, M.D. James Graham Brown Cancer Center Department of Medical Oncology

2. Learning objectives • Help overcome certain paradigms of alternative medicine. • Understand the history of acupuncture and its principles. • Mechanism of action • Barriers in scientific research • Review recent studies of its implementation to modern medicine in the cancer setting.

3. Acupuncture background • Practice has more than 4,000 year of empirical evidence. • Han dynasty made an effort to elaborate treatment compilation circa 200 B.C.. • Huangdi Neijing: Yellow Emperor’s Classic of Internal Medicine • Portuguese missionaries in the 16th century introduced the idea to Europe. • Willem ten Rhijne wrote first text in 1683.

4. Understanding acupuncture Traditional Chinese principle • Body consists of 12 systems or channels through which qi circulates. • Solid systems and hollow systems. • Lung, large intestine, stomach, spleen, heart, small intestine, bladder, kidney, pericardium, gall bladder, liver and san jiao. • Health is determined by the balance of the yin and yang. • A block or stagnation of flow creates illness. • Stimulation of key points can restore qi flow.

5. Acupuncture points

6. Acupuncture in recent times • In 1822 the Chinese emperor banned the practice at the Imperial Academy of Medicine. • Associated with low class and illiterates. Mao Zedong and Nixon effect

7. How do you integrate acupuncture concepts to conventional medicine?

8. Modernizing acupuncture “a family of procedures involving stimulation of anatomic locations on the skin by a variety of techniques. The most studies… uses penetration of the skin by thin, solid, metallic needles, which are manipulated manually or by electrical stimulation.” NIH Goals • Understand mechanism of action • Standardize practice and clinical research Organisms • Office of Alternative Medicine (OAM) • National Center for Complementary and Alternative Medicine (NCCAM) National Institute of Health

9. Problems in standardization • Factors affecting quality • Setting • Poor study design • quality control employed • lack of detailed report • Variants of treatment employed • Deficiencies in available studies • Designed by clinicians not trained in clinical trial design. • Most studies had randomization only but lacked blinding. • No mention of patient withdrawal. • Lack of tool to standardize quality scales. • Variation in acupuncture technique. Hematol Oncol Clin N Am 22 (2008)

10. Problems in standardization • Placebo issues and the de qi sensation. • Placebo needle (Streiberger needle) • Insertion at different site • Variation during acupuncture performance. • Operator’s experience Hematol Oncol Clin N Am 22 (2008)

11. Problems in standardization

12. Standardization • STRICTA • Standards for Reporting Interventions in Controlled Trials of Acupuncture • Guidelines to structure report of intervention to facilitate transparency, enable interpretation and facilitate replication. • Founded in 2001 • Revised 2010 with conjunction of CONSORT group and the Chinese Cochrane Centre. Acupunct Med June 3, 2010

14. How does it work?

15. Thin pain fibers Large pressure, vibration fibers Dorsal horn Transmission cells Inhibitory cells Mechanism of action • Basic concept • Based on stimulation of the neuroendocrine system involving the central and peripheral nervous system and the response is generates. • Melzach-Wall gate theory of pain Wang SM et al. Anesth Analg 2008 106(2)

16. Mechanism of action (cont’d)

17. MGH group (cont’d) Sample: • 15 right handed acupuncture naive MGH volunteers. • No medications, no illness, no neurological or mental issues. Objective: • To observe fMRI brain images after stimulation of ST-36 point using regular acupuncture vs pressure. Method:

18. MGH Group (cont’d) Results:

19. MGH Group (cont’d)

20. MGH Group (cont’d) Conclusions: • There is an integrated response of the human cerebro-cerebellar and limbic systems to acupuncture point ST 36. • Each pressure stimulation elicits distinct changes in imaging studies. • Brain response varies depending on de qi. Limitations: sample size, confounding factors, experimental control and temporal effects.

21. Other studies for MOA • Han JS et al. Trends Neurosci 2003 • Studied neuropeptide release produced by electrical stimulation at different frequencies. Contribution: • It is possible to facilitate the release of certain neuropeptides in the CNS by means of peripheral electrical stimulation. • opioidergic and/or monoaminergic neurotransmission involving the brainstem, thalamus, and hypothalamic function. • Liang XB et al. Brain Res Mol Bran Res 2002 • Studied the effect of electroacupuncture of dopaminergic neurons in midbrain. • Contribution: • Acupuncture stimulation moderates a network of brain regions including somatosensory, cortices, amygdala, hippocampus and hypothalamus.

22. Other studies for MOA (cont’d) • Napadow V et al. Neuroimage 2009 • Studied prolonged acupuncture activity modulation in the brainstem using fMRI and PET scans. Contribution: • There is a linearly decreasing time-variant activation, suggesting classical habituation in sensorimotor brain regions • Bimodal time-variant activity in the limbic region. FURTHER STUDIES ARE STILL NEEDED TO UNDERSTAND ITS MECHANISM

23. Implementing acupuncture in cancer treatment

24. Studied areas • Chemotherapy induced nausea • Sensory neuropathy • Post surgical pain • Radiation induced xerostomia • Aromatase inhibitor associated arthralgias • Chemotherapy induced neutropenia

25. Chemotherapy induced nausea

26. Shen J et al. 2000;284(21)

27. Shen J et al. (cont’d) • Study: • three arm, parallel group, randomized controlled study. • Objective: • To compare the effectiveness of electroacupuncture vs minimal needling and mock electrical stimulation or antiemetic medications alone in controlling emesis among patients undergoing a highly emetogenic chemotherapy regimen. • Patients: • 104 women with high-risk breast cancer.

28. Shen J et al. (cont’d) N=37 Low frequency electroacupuncture N=33 Cyclophosphamide Cisplatin Carmustine 104 women with Breast cancer Mock electrostimulation N=34 • prochlorperazine • lorazepam • diphenhydramine No adjunct needling Acupuncture points used: PC6 and ST36

29. Results

30. Results

31. Results (cont’d)

32. Conclusions • Adding a daily electroacupuncture procedure to pharmacotherapy was more effective than pharmacotherapy alone in preventing chemotherapy-induced emesis. • The positive effects wear off if acupuncture is not continued as seen during follow-up period. • Note: minimal needling led to a reduction in the frequency of emesis episodes. • Patient attention and the clinician-patient interaction?

33. Sensory neuropathy

35. Alimi D et al. • Study: • three arm, blinded, randomized, controlled study, with two placebo arms. • Objectives: • To compare the effect of acupuncture needles in true-point sites vs a non-effective acupuncture. • Insertion of acupunture needles in acupunture points alleviates pain symptoms. • Patients: • 90 acupuncture naive patients from the Institut Gustave Roussy with neuropathy after chemotherapy treatment.

36. Alimi D et al. N=29 Acupuncture Uncontrolled pain and > 1 month on analgesics N=30 • one month evaluation and reposition of needles. 90 patients with neuropathy Acupuncture at placebo sites N=31 Fixed seeds Patients where taken off study if pain regimen was changed due to uncontrolled pain.

37. Results

38. Results (cont’d) Note: p value <0.001

39. Conclusions • Auricular acupuncture at points where an electrodermal signal is detected is associated with a significant reduction in pain intensity in patients with neuropathic pain. • A reduction in pain is associated with a decline in the average electrical signal detected at ear points. • No effect of the placebo treatments whether they implied skin penetration or not. • Chronic pain may be less susceptible to placebo effects than an acute pain.

40. Post surgical pain

41. J Clin Oncol 2010 Vol 28(15)

42. MSKCC Group • Study: • Prospective, open-label, randomized controlled trial. • Objectives: • To determine whether acupuncture reduces pain and dysfunction in patients with cancer with a history of neck dissection. • To determine whether acupuncture relieves dry mouth in this population. • Patients: • 58 patients from Memorial Sloan-Kettering Cancer Center who underwent neck dissection and had moderate to severe pain.

43. MSKCC Group (cont’d) • Acupuncture treatment: • one a week x 4 wks • LI-4 • SP-6 • GV-20 • luozhen • auricular shenman

44. MSKCC Group (cont’d)

45. Results

46. Results (cont’d) P < 0.001

47. Conclusions • Significant reductions in pain, dysfunction, and xerostomia were observed in study patients receiving acupuncture versus usual care. • The reduction in medication was not statistically significant. (p = 0.4) • Problems with study: • patients were not blinded

48. Radiation induced xerostomia

50. San Diego Group • Study: single arm. • Objectives: • To describes the use of acupuncture as palliation in patients with xerostomia secondary to XRT for head and neck cancer. • Patients: • 18 patients who underwent bilateral radiation treatment for HN cancer and developed xerostomia refractory to pilocarpine. • Received 60 - 70 cGy.