Integrative Treatment of Ovarian Cancer Stage III

Full title: “The Integrative Medical Treatment of Ovarian Cancer Stage III: A Case Study”

Abstract

Ovarian cancer is the most lethal cancer of the female genital system worldwide¹. In the last 10 years survival rates (SR) of ovarian cancer patients have not improved: typical SR of stage III ovarian cancer patients are between 2-5 years². Integrative medicine offers an opportunity for ovarian cancer patients to incorporate other modalities of treatment into their care. This case study examines an integrative medicine treatment of a Stage IIIA high grade serous carcinoma ovarian cancer patient with acupuncture, Chinese herbal medicine, and qigong from the time of diagnosis in 2016 through 2022. Over the past six years, this patient has had improved symptoms – including maintaining a low CA-125 level – and lived past the typical 5-year period of patients with similar forms of ovarian cancer. Further research is needed to determine if an improvement to survival rate of ovarian cancer patients could be achieved when integrative medicine incorporates acupuncture, Chinese herbal medicine, and qigong into treatment.

Introduction

Ovarian cancer (OvCa) is the 7^th leading cancer in women, and the most frequently diagnosed lethal malignancy of the female genital system worldwide^{1, 3}. There are approximately 239,000 new cases and 152,000 deaths worldwide per year¹. Standards of care for treatment involve first surgery and then post-surgical chemotherapy or radiation.

The first most common type of cancer to utilize integrative medicine is breast cancer; the second being OvCa^{4, 5}. Acupuncture and Chinese herbal medicine (CHM) are among the most common types of integrative medicine treatments used for breast and OvCa. Within the large variety of integrative medicine treatments, the most recommended by gynecologic oncologists are exercise, nutritional therapy, dietary supplement, herbal medicines, and acupuncture⁶. However, there is limited research on acupuncture and CHM as an integrative medical treatment for OvCa. This case study examines the integrative medical treatment of a Stage IIIA OvCa patient with high grade serous carcinoma of the left and right ovaries. Integrative modalities utilized in this case study include acupuncture, CHM, and qigong.

Biomedical

Experts agree that there is a lack of early detection for diagnosis of OvCa⁷. Diagnosis involves a combination of symptom monitoring and gynecological examination or imaging and analysis of risk factors such as BRCA1 gene mutations^[1]. OvCa may first be detected upon gynecological exam when masses may be palpated on the ovaries or fallopian tubes.

Symptoms of OvCa involve a combination of abdominal bloating and swelling, pain in the abdomen or pelvis, difficulty eating, feeling full quickly, lack of appetite, an urgent need to urinate, frequent urination, change in bowels pattern, change in menses, bleeding between menstrual cycles, lumbago, fatigue, and gain or loss of weight⁷. Blood markers such as CA-125 are produced by advanced ovarian epithelial cell cancers but are not always reliable for early detection. In 20% of advanced OvCa and 50% of early-stage disease, CA-125 is not elevated⁸. CA-125 is significant in monitoring progression or remission of the disease in advanced stages of OvCa⁸.

Current research focuses on earlier detection of cancer as “survival rates for women with early-stage ovarian carcinoma range from 70% to 90% compared with 20–30% for women with advanced disease”⁷. The International Federation of Gynecology and Obstetrics classified OvCa diagnosis into stages known as FIGO stages, with 84% of patients presenting as stage IIIC at time of initial diagnosis⁹. In Zhang’s 2020 study the pathologic stage of diagnosis was also found to be an independent prognostic factor for OvCa patients, with a higher stage having a poor disease-free stage and lower survival rate (SR)³. “According to the NIH Surveillance, Epidemiology, and End Results program (SEER) survival statistics (2009–2015), 5-year survivorship of OvCa is only 47.6%, which remained virtually unchanged since the last decade”².

Chinese Medicine Background

The concept of tumor or liu 瘤 was discovered on oracle bone engravings and tortoise shells dating back to the Shang Dynasty (16^th – 11^th century B.C.), which points to an ancient concept of cancer¹⁰. Many classical texts discussed the etiology of these masses, with the earliest Chinese medicine (CM) text being the Huang Di Nei Jing compiled during the Warring Period (475-221 B.C.)¹¹. In the Ling Shu portion of the Huang Di Nei Jing, there are descriptions of shijia (shi = stone; jia = mass) or as translated by Paul U. Unschuld as “stone conglomerations”^[2]12. In Zhu Bing Yuan Hou Lun, dated 610 A.D., Chao Yuanfang differentiated between two kinds of abdominal masses: Zheng masses, which are immovable, and Jia masses, which are movable^{[3] 11}.

In CM, the development of OvCa is associated with qi stagnation, blood stasis, cold congealing, and accumulation of dampness in the body. Irregularities in one’s diet can cause weakness and damage to the Spleen and Stomach which, in turn, causes damp-heat conglomerations. Eventually, the zang–fu organs will be imbalanced and lead to deficiency of qi and blood¹³. In CM, the treatment of cancer will invariably be related to one’s vital/zheng qi, which can be correlated to our immune system¹¹.

Table 1.

Ovarian Cancer – Pattern Identification and treatment¹¹

Case Description

Case History

This 59-year-old female patient presented with the chief complaint of abdominal pressure, sharp spinal pain, an abdominal mass, abdominal bloating, abnormal vaginal discharge, and fatigue. A blood test revealed a CA-125 level of 135. Further testing classified the Ovarian Carcinoma as a high-grade serous carcinoma of the left ovary mass measured 9x8x6 cm and a right ovary high grade serous tumor measuring 1.5 cm in diameter. A left para-aortic biopsy revealed metastatic high grade serous cells in two out of the four lymph nodes. Microscopic peritoneal metastases beyond the pelvis were also discovered.

A bilateral ovariectomy and hysterectomy were performed to remove the cancerous tissue. Proposed chemotherapy by the oncologist was carboplatin and Taxol. The patient declined chemotherapy and opted for continued monitoring of CA-125 levels, PET scans, and integrative treatment with CM including acupuncture, CHM, and qigong. In 2019 a hotspot on the PET scan image and elevation of the CA-125 to a 16 suggested cancer in a lymph node. The lymph node, which was enlarged to 2.5 cm, was removed in December of 2019. April 2022 lab results indicated a current CA-125 of 10. The patient is BRCA gene positive.

Treatment

The patient received acupuncture about an average of once a month from September 2016 to present, and a typical treatment time of 50 minutes. The acupuncture points are summarized below (Table 2.). The cumulative actions of the acupuncture treatment were to dispel toxic damp heat from the lower jiao, tonify blood, dispel blood stasis, smooth Liver qi, and tonify the Spleen. Smokeless moxa was applied from time to time. Pine disposable stainless steel needles were used, 30mm in length, 34 gauge. The patient also maintained a daily one-hour qigong practice to promote the flow of qi and supplement her monthly acupuncture treatments. The patient practiced Dayan/Wild Goose qigong as instructed by her CM Doctor.

Table 2.

Acupuncture points used to dispel toxic damp heat from the lower jiao, tonify blood, dispel blood stasis, smooth Liver qi, tonify Spleen.¹⁵

Based on the initial exam in 2016, the patient exhibited a red tongue tip with a darkish black root and thick yellow coat and a deep center crack (Figure 1.). In the patient’s right pulse, the Kidney position was fast and rapid (indicating heat), and the Spleen/Stomach was slippery (indicating dampness), the Lung pulse felt weak (indicating deficiency in zheng qi). In the left pulse, the Heart/Small Intestine was slightly rapid (indicating heat), the Liver/Gall Bladder pulse was stringy and fast (indicating stagnation), and the left Kidney pulse was weak and deficient (indicating injury to the zheng qi). The tongue’s yellow coat indicated dampness and heat, the red tongue body indicated heat, and the black root indicated toxic heat that burns the blood, causing stagnation¹⁴.

The initial 2016 OvCa diagnosis, in terms of CM, was toxic damp heat of the lower jiao (uterus) burning the blood to create stasis, Liver qi stagnation, and Spleen qi deficiency. According to Li (2003), the nature of cancerous tumors indicates toxic heat and dampness¹¹. The root of the heat toxin in this patient comes from both stagnation and deficiency. The deficiency of the Spleen failing to transform and transport fluids lead to the buildup of dampness. When fluid is congested and dampness builds, this results in heat. The symptoms that indicated heat and dampness with a root in deficiency are abdominal bloating, fatigue, vaginal discharge, fast and slippery pulse in the right guan and chi positions. Blood stagnation is indicated by the sharp spinal pain. Stagnation is further complicated by emotional stress which stagnates the Liver qi and prevents free flow of qi. The patient’s abdominal mass is the physical manifestation of the dampness and stagnation which congealed to form a fixed mass known in ancient China as a Zheng Jia¹¹. The modified formula Huang Lian Jie Du Tang (Table 3.) was prescribed to dispel toxic damp heat from the lower jiao/space, tonify blood, dispel blood stasis, smooth Liver qi, and tonify the Spleen. Herbs in this formula focused specifically on clearing the heat toxin of the tumor such as bai hua she she cao (Hedyotis Diffusae Herba), huang bai (Phellodendri Cortex), and huang lian (Coptidis Rhizome). Ming Tong or KPC brand herbs were prescribed based on availability in granules. All prescriptions were 4 grams, BID with 3 ounces of hot drinking water and on an empty stomach.

Table 3.

Huang Lian Jie Du Tang (Coptis Decoction to Resolve Toxicity) modified formula¹⁶ – September 2016

In a 2019 PET scan, the patient was found to have an elevation in CA-125 which resulted in a subsequent surgery to remove a cancerous lymph node. At that time, the color of the tongue was more red and the coating was thin and white, indicating heat and dampness in the interior. After the additional cancerous lymph node was discovered and removed in 2019, the herbs were adjusted to reflect the changes in the patient’s condition. Modified Gui Zhi Fu Ling Wan (Cinnamon Twig and Poria Pill) and Xiang Sha Yang Wei (Nourish the Stomach Decoction with Aucklandia and Amomum) was prescribed to transform the blood stasis, further strengthen the Spleen and Stomach, resolve dampness, and move fluids through strengthening the digestion and vital/zheng qi (Table 4.). Herbs continue to address the heat toxin of the cancer such as pu gong ying (Taraxaci Herba), and ze xie ((Alismatis Rhizoma) (Table 4.). In October of 2019 huang qi (Astraguli Radix) was added to support the vital/zheng qi.

Table 4.

Gui Zhi Fu Ling Wan (Cinnamon Twig and Poria Pill) and Xiang Sha Yang Wei (Nourish the Stomach Decoction with Aucklandia and Amomum) modified formula¹⁶ – August 2019

Table 5.

Liu Wei Di Huang Wan (Six-Ingredient Pill with Rehmannia) modified formula¹⁶ – April 2020

In 2021 the tongue and pulse changed in the patient both due to progression of treatment and increased age. As a person ages, the yin and yang energies of the Kidney decline and is reflected in the reduction of coat in the front of the tongue and the transverse and lateral cracks in the tongue. The swelling and teeth marks in the tongue reflect Spleen deficiency while the rear of the tongue body was dusky, which indicated stagnation (Figure 2.). The progression of the root color from black to dusky points to a reduction of blood stagnation. The thinner rear yellow coating still shows a lingering amount of dampness and heat. The reduction of the thickness of the tongue coat indicated an improvement in the patient’s damp condition and the change of dirty yellow color to white-yellow indicated a reduction in heat (Figure 2.).

In April 2021 the formula was modified to address the changes in age and Liu Wei Di Huang Wan (Six-Ingredient Pill with Rehmannia) was added in order to clear heat from deficiency (Table 5.). Additional herbs were prescribed to continue to address the heat toxins which were present due to the possibility of the recurrence of cancer. By preventing the buildup of heat toxins, the formation of additional tumors or metastasis could be suppressed. The direction of treatment continued to address Liver stagnation and to move blood to prevent blood stagnation. The new formula also focused on supporting the patient’s vital/zheng qi and yin essence to assist the body’s natural ability to suppress tumor formation.

In May of 2021, after one month of the herbs, the patient’s tongue showed continued improvement (Figure 3.) The change of coat color from yellow to white demonstrated a clearing of heat and a reduction of toxicity. The tongue body color had a pinker color, which also indicated a reduction of heat and stagnation. Swelling in the tongue and edges in addition to teeth marks indicated a continued need to address the underlying Spleen qi deficiency and dampness.

Outcomes and Prognosis

As treatment progressed, the diagnostic patterns improved. Change as was visible in the patient’s tongue, blood work, and symptoms. As the toxic heat resolved the tongue improved and the black coating at the rear cleared (Figure 1.). The changes in the tongue indicate the clearing of heat, increased flow of blood, and an improvement in the health of the patient (Figure 3.). At the time of initial diagnosis, the patient’s CA-125 level was 135 with a normal CA-125 level range being 0 to 35. Post hysterectomy the CA-125 level reduced to 13. As Chinese medicine treatment continued the CA-125 level remained low between 11 to 16. Current PET scans remained clear. The typical SR of an OvCa patient diagnosed at Stage IIIA is 2-5 years with the rate of 5-year survival at 47.6%². Currently this patient has survived for 6 years after her initial diagnosis in 2016 surpassing the typical SR.

Conclusion

Although research continues in OvCa, SRs of patients have not increased over the last 10 years. A lack of early diagnosis contributes to a lower SR with the majority of cancers diagnosed at Stage III. This Stage IIIA OvCa patient survived past the 5-year period and incorporated the integrative medical treatments acupuncture, CHM, and qigong. Further research of integrative medicine utilizing CM treatments for Stage IIIA OvCa patients is needed to determine if the outcomes of this case can be reproduced.

References

1. Yoshihara, K., Enomoto, T., Aoki, D., Watanabe, Y., Kigawa, J., Takeshima, N., Inomata, H., Hattori, K., Jinushi, M., Tsuda, H., & Sugiyama, T. (2020). Association of gBRCA1/2 mutation locations with ovarian cancer risk in Japanese patients from the CHARLOTTE study. Cancer Science, 111(9), 3350–3358. https://doi.org/10.1111/cas.14513
2. Li, M., Cheng, X., Rong, R., Gao, Y., Tang, X., & Chen, Y. (2020). High expression of fibroblast activation protein (FAP) predicts poor outcome in high-grade serous ovarian cancer. BMC Cancer, 20(1), 1032. https://doi.org/10.1186/s12885-020-07541-6
3. Zhang, Y., Ye, Q., He, J., Chen, P., Wan, J., Li, J., Yang, Y., & Li, X. (2020). Recurrence-Associated Multi-RNA Signature to Predict Disease-Free Survival for Ovarian Cancer Patients. BioMed Research International, 2020, 1618527. https://doi.org/10.1155/2020/1618527
4. Morris, K. T., Johnson, N., Homer, L., & Walts, D. (2000). A comparison of complementary therapy use between breast cancer patients and patients with other primary tumor sites. The American Journal of Surgery, 179(5). https://doi.org/10.1016/S0002-9610(00)00358-5
5. Gansler, T., Kaw, C., Crammer, C., & Smith, T. (2008). A population-based study of prevalence of complementary methods use by cancer survivors. Cancer, 113: 1048-1057. https://doi.org/10.1002/cncr.23659
6. Klein, E., Beckmann, M. W., Bader, W., Brucker, C., Dobos, G., Fischer, D., Hanf, V., Hasenburg, A., Jud, S. M., Kalder, M., Kiechle, M., Kümmel, S., Müller, A., Müller, M.-A. T., Paepke, D., Rotmann, A.-R., Schütz, F., Scharl, A., Voiss, P., … Hack, C. C. (2017). Gynecologic oncologists’ attitudes and practices relating to integrative medicine: results of a nationwide AGO survey. Archives of Gynecology and Obstetrics, 296(2), 295–301. https://doi-org.ciis.idm.oclc.org/10.1007/s00404-017-4420-y
7. Goff, B. A., Mandel, L., Muntz, H. G., & Melancon, C. H. (2000). Ovarian carcinoma diagnosis. Cancer, 89(10), 2068–2075. https://doi.org/10.1002/1097-0142(20001115)89:10<2068::AID-CNCR6>3.0.CO;2-Z
8. CA-125 Blood Test Alone Does Not Diagnose Ovarian Cancer. (n.d.). Ovarian Cancer Research Alliance. Retrieved March 9, 2022, from https://ocrahope.org/patients/about-ovarian-cancer/symptoms-and-detection/what-is-ca-125/
9. Javadi, S., Ganeshan, D. M., Qayyum, A., Iyer, R. B., & Bhosale, P. (2016). Ovarian Cancer, the Revised FIGO Staging System, and the Role of Imaging. American Journal of Roentgenology, 206(6), 1351–1360. https://doi.org/10.2214/AJR.15.15199
10. Liu, J., Wang, S., Zhang, Y., Fan, H. T., & Lin, H. S. (2015). Traditional Chinese medicine and cancer: History, present situation, and development. Thoracic Cancer, 6(5). https://doi.org/10.1111/1759-7714.12270
11. Li, P. (2003). Management of Cancer with Chinese Medicine. Netherlands: Donica Publishing Limited.
12. Unschuld, P. (2016). Huang Di Nei Jing Ling Shu (2nd ed.). University of California Press., p. 536
13. Li, Z. Z. (2006). Indispensable Medical Reading. People’s Medical Publishing House, Beijing.
14. Maciocia, G. (2021). Tongue Diagnosis in Chinese Medicine – Third Edition (3rd edition). Eastland Press.
15. Deadman, P., Al-Khafaji, M., & Baker, K. (2007). A manual of acupuncture. Journal of Chinese Medicine Publications.
16. Scheid, V., Bensky, D., Ellis, A., & Barolet, R. (2009). Chinese Herbal Medicine: Formulas & Strategies (2^nd Ed.). Seattle, WA: Eastland Press, Inc.
17. Huang, J.-Y., Yang, S.-F., Wu, P.-J., Wang, C.-H., Tang, C.-H., & Wang, P.-H. (2021). Different Influences of Endometriosis and Pelvic Inflammatory Disease on the Occurrence of Ovarian

Cancer. International Journal of Environmental Research and Public Health, 18(16). https://doi.org/10.3390/ijerph18168754

1. Family and genetic history can indicate a need for increased and early screening. Familial risk factors include a blood relative with a history of breast or ovarian cancers, Ashkenazi Jewish ancestry, a personal history of breast cancer prior to age 40, or a personal history of breast cancer prior to age 50 in combination with another risk factor. Genetic history risk factors include being a carrier of the BRCA1 gene, the BRCA2 gene, or a gene mutation known as Hereditary Non-Polyposis Colon Cancer (HNPCC)/Lynch syndrome [9]. “It has been recently estimated that approximately 44% of women who inherit gBRCA1 mutations and approximately 17% of those who inherit gBRCA2 mutations will develop ovarian cancer by 80 years of age”[1]. A history of endometriosis is also considered to be a risk factor as higher incidence of OvCa has occurred in patients with a prior history of endometriosis [17]. ↑
2. Paul U. Unschuld provides a translation of the Huang Di Nei Jing Ling Shu’s description of such a mass.Stone conglomerations develop in the [uterine] bladder. Cold qi has settled at the mouth of the uterus. The mouth of the uterus is closed and cannot be penetrated by qi. When malign blood that should be drained fails to be drained, lumps of blood remain inside. They increase in size day by day, as if [that person] were pregnant. The monthly period fails to descend in time. [Such conglomerations] emerge in women only. They can be led away downward¹². ↑
3. t ↑

Acknowledgements 

The patient has consented to the use of her medical information and tongue images for the purpose of this paper and publication. 

The authors acknowledge that the patient in this Case Study is and was a patient of Dr. Erlene Chiang at her Chinese medicine and martial arts clinic. The patient was also a patient of the Oncology class at the American College of Traditional Chinese Medicine and received Chinese herbal formulas prescribed by Dr. Chiang, Dr, Leddy, and Dr. Jackson.