A Pilot Survey of Integrative Oncology in Hospitalized Children Undergoing Aggressive Therapy for Cancer and Blood Disorders at a Single Pediatric Cancer Center

Abstract

Objectives:

To assess treatment modalities and patients’ attitude regarding integrative oncology with a special focus on Kampo in hospitalized children for hematological diseases and solid tumors.

Methods:

All children who were hospitalized for hematological or oncological diseases at the Department of Pediatrics, Nagoya University Hospital, between January 25 and February 25, 2018, were invited to participate in this prospective survey.

Results:

Forty-eight patients responded to the survey. These included 27 patients aged ≤6 years, 11 aged ≥13 years, and 10 aged 7 to 12 years; 19 were diagnosed with a hematological malignancy, 9 with a nonmalignant hematological/immunological disease, and 20 with solid tumors. In all, 42% of patients were administered pharmaceutical-grade Kampo extracts, and 80% reported high effectiveness. Other modalities were used much less frequently. Oral administration of herbal extracts was challenging in children treated with Kampo. Integrated use of Kampo in pediatric hematology/oncology was desired in 77%, and 79% wished for more information about Kampo. In all, 90% desired to be seen by a pediatric hematologist/oncologist specializing in Kampo.

Conclusion:

Contribution of Kampo to pediatric hematology/oncology was highly appreciated during aggressive therapy for cancer and blood disorders.

Introduction

Recent advances in pediatric hematology and oncology have improved overall survival and life expectancy in children with cancer and blood disease.^1,2 Nevertheless, these children still suffer from invasive treatments and bear a significant social and emotional burden. Effective multidisciplinary care is required, ³ and integrative oncology (IO) may effectively alleviate cancer-related symptoms in children. ⁴ Herbal remedies are the most common modality used to support anticancer treatment. ⁵ Additional modalities are increasingly being integrated into routine North American and European pediatric care.^6,7 Kampo medicine, a form of East Asian traditional herbal medicine, is the orthodox medicine in Japan that was used since the sixth century till western medicine took over in the late 19th century. Although Kampo encompasses acupuncture, moxibustion, and massage, it refers primarily to prescribing herbal formulas. Kampo is taught in medical schools, and herbal formulas are available as regulated pharmaceutical-grade extracts exclusively prescribed by physicians. Board certification has been established for Kampo specialists. ⁸ Standardized herbal formulas are prescribed based on clinical studies. However, treatment may be personalized to match disease patterns with formulas based on traditional methodology and practice. ⁹ Kampo is integrated into the national health care system as supportive care for cancer patients in Japan.^8,10 Nearly 60% of Japanese physicians prescribe Kampo for adult cancers. ¹¹ Although Kampo’s 146 pharmaceutically standardized formulas are covered by Japanese National Health Insurance, and therefore, are readily prescribed by physicians, pediatric hematologists/oncologists are not generally educated about the use of Kampo. This study aimed to assess treatment modalities and patients’ attitudes regarding IO with a special focus on Kampo during hospitalization.

Methods

All children who were hospitalized for hematological or oncological diseases at the Department of Pediatrics, Nagoya University Hospital, between January 25 and February 25, 2018, were included in the study. The hospital employed a pediatric hematologist/oncologist who specialized in Kampo. No independent department and team were responsible for IO, and it was not officially offered to inpatients. The patients or their guardians were invited to participate in the prospective survey. The questionnaire was paper-based and designed to be self-administered. Section 1 asked 4 questions regarding patient characteristics. Section 2 included 11 questions and 2 free text boxes regarding usage and subjective effectiveness of prescribed Kampo, acupuncture/moxibustion/shonishin, over-the-counter (OTC) herbal medicine, and other modalities (nutritional, psychological, and physical modalities). The patients or their guardians were asked whether treatment modalities as a whole were effective, and then asked what specific symptoms, if any, were alleviated. Section 3 included 3 questions regarding physicians’ subspecialty and 4 questions regarding patients’ needs for Kampo. Section 4 was a free comment field. The effectiveness questions were answered on a scale, and the answers were converted to 5 ordinal variables at analysis. A score ≥50% was considered effective. Statistical analysis was conducted using JMP Pro 15.0.0 (SAS Institute Inc., NC). The Kruskal-Wallis test was used for ordinal variables and Fisher’s exact test was used for categorical variables. A P value of <.05 was considered statistically significant. The ethics committee of Nagoya University Graduate School of Medicine approved this study (approval number: 2017-0455).

Results

Fifty-three questionnaires were provided, one per each patient, and responses were received for 48 (91%) of them. There were 27 (56%) patients aged ≤6 years, 11 (23%) aged ≥13 years, and 10 (21%) aged 7 to 12 years; 19 (40%) were diagnosed with a hematological malignancy, 9 (19%) with a nonmalignant hematological/immunological disease, and 20 (42%) with solid tumors. Of all, 42% received a hematopoietic stem cell or solid organ transplant. Most questionnaires were completed by the patients’ guardians except for 5 aged ≥13 years who answered themselves.

In all, 20 (42%) were administered pharmaceutical-grade Kampo extracts, and 2 used acupuncture and shonishin, a non-needle type of acupuncture. OTC herbal medicine and other forms of integrative medicine were used in 4 (8%) and 5 (10%) cases, respectively (Figure 1A). Kampo extracts were felt to be effective in 16 of 20 patients (80%). Effectiveness was reported in hematuria, diarrhea, and limb dysesthesia. Two of the 4 who reported low effectiveness attributed this to difficulty in using oral Kampo. One of the 3 patients who used OTC reported high effectiveness, as did 2 of the 5 who used other integrative medicine (Figure 1B).

Figure 1.

Use of and desire for integrative oncology in children with cancer and blood diseases. (A) Use of integrative medicine in inpatient children with cancer and blood disorders. Other integrative medicine included nutritional (eg, ketogenic diets, dietary supplements, and herbs excluding Kampo), psychological (eg, mindfulness, music, and art therapies), and physical modalities (eg, massage, yoga, and dance). (B) Subjective effectiveness of integrative medicine. The effectiveness questions were answered on a scale, and the answers were converted to 5 categories. (C) Need for Kampo integration and information. (D) Need for pediatric hematologists/oncologists specializing in Kampo and Kampo specialists without hematology/oncology specialty. Abbreviations: OTC, over-the-counter medicines; heme/onc, hematology and oncology.

Of the 38 who answered questions regarding administering Kampo to children, 30 (63%) reported difficulty using oral herbal extracts, and 28 (58%) preferred capsules and tablets. Ten (21%) patients refused Kampo formulas, mostly due to their taste and smell.

Only 6 of 48 patients (13%) knew about board certification for Kampo specialists, whereas 15 (31%) knew of board certification for pediatric hematologists/oncologists (P = .006). The perception of unmet needs for Kampo was investigated and described in Figure 1C and D. Integrated use of Kampo in pediatric hematology/oncology was desired in 37 (77%) of 48, and 38 (79%) wished for more information about Kampo (Figure 1C). Of all 48, 43 (90%) wanted to be seen by a pediatric hematologist/oncologist specializing in Kampo. However, only 10 (21%) desired to be seen by a Kampo specialist who was not specialized in pediatric hematology/oncology (P < .0001, Figure 1D).

All comments in the free text box were extracted and retrospectively categorized into 4 groups: (1) The impression of Kampo (well-tolerated medicine vs concerns about possible interactions); (2) Expectations for reducing the adverse effects of chemotherapy/radiotherapy; (3) Expanded treatment options and effects not possessed by conventional therapy; (4) Challenges in taking oral Kampo.

Discussion

Despite a high prevalence of IO for children worldwide,^5,7,12 this is the first study to investigate Kampo and IO use in children admitted to a children’s cancer center in Japan. Prescribed Kampo was more frequently used in this study than other IO modalities. Overall, patients’ families felt that the benefits of Kampo outweighed the disadvantages. Nearly 90% of the guardians wished to see more integration of Kampo into pediatric hematology/oncology. This high rate of usage and demand for pediatric Kampo are consistent with recent IO studies in German and Swiss children, although homeopathy was the leading modality and was not necessarily covered by health insurance.^6,12 Patients’ guardians felt that the effectiveness of prescribed Kampo was relatively high, suggesting a role for Kampo specialists. Oral administration of herbal extracts was challenging in children treated with Kampo, consistent with treatment for nonmalignant disease. ¹³ This study demonstrated that patients and their families were unaware of the distinctive medical system regarding Kampo treatment. A feature that may limit generalization of the study findings is the recruitment of few patients in a single institute where IO, including Kampo, was not systematically offered.

In conclusion, multidisciplinary cooperation is warranted in the treatment of children with cancer and blood disorders. Kampo’s contribution was highly appreciated by children and their guardians.