ZHANG Gui-qiong (张桂琼), ZHANG Qiang (张 强), HAN Peng-bing (韩鹏炳),GAO Li-ying (高力英), KANG Miao (康 苗)

1. Department of Integrated Traditional Chinese and Western Medicine, Gansu Provincial Cancer Hospital, Lanzhou 730050, China

2. Department of Urology, Gansu Provincial Cancer Hospital, Lanzhou 730050, China

3. Department of Radiotherapy, Gansu Provincial Cancer Hospital, Lanzhou 730050, China

ABSTRACTObjective:To observe clinical efficacy of Lanzhou Formula (兰州方) with Bingpeng Powder(冰硼散) mouthwash in preventing and treating radiation-induced oral mucositis.Methods:A total of 200 patients with malignant tumors in the head and neck who received radiotherapy in our hospital from April 2018 to April 2020 were selected as research objects, and they were randomly divided into the study group and control group. The control group was given radiotherapy combined with mouthwash, which consisted of 500 mL of normal saline, 125 mg of vitamin B12, 400 000 U of gentamicin and 1 g of lidocaine. The study group was given radiotherapy combined with Lanzhou Formula with Bingpeng Powder mouthwash.Incidences of radiation-induced oral mucositis, chewing and swallowing functions, and Karnofsky (KPS)scores were compared between the 2 groups.Results:At the end of the radiotherapy, there was no Grade 4 radiation-induced oral mucositis in the 2 groups. Compared with the control group, the radiation-induced oral mucositis in the study group basically belonged to Grade 1 and Grade 2, with a lower incidence of Grade 3 (P＜0.05). At the end of the radiotherapy, the chewing and swallowing functions in the 2 groups were decreased, but patients with 2-point chewing and swallowing functions in the study group were more than those in the control group, and patients with the 3-point were less than those in the control group (P＜0.05).At the end of the radiotherapy, the KPS scores were decreased, but those in the study group were higher than those in the control group (P＜0.05).Conclusion:During radiotherapy for patients with malignant tumors in the head and neck, Lanzhou Formula with Bingpeng Powder mouthwash can decrease the severity of radiation-induced oral mucositis, protect chewing and swallowing functions of patients to a certain extent,and improve the general condition of patients. It is worthy of clinical application and promotion.

KEYWORDS Lanzhou Formula; Bingpeng Powder; Radiation-induced oral mucositis

In recent years, the incidence of malignant tumors in the head and neck has gradually increased, and can account for about 30% of the incidence of all malignant tumors, which seriously threatens people's health and life safety[1]. In clinical practice, radiotherapy is mainly used to control local tumors of patients with head and neck malignant tumors, thereby improving the overall survival rate of the patients. However, radiation ionization can also damage normal cells of the body while destroying tumor cells, leading to local or even systemic adverse reactions, which is not conducive to improving the quality of life[2,3]. Oral mucositis is a relatively common type of complications, which increases suffering of patients as well as their mental and economic burdens and decreases their quality of life. Therefore, measures that should be taken to actively prevent and treat radiation-induced oral mucositis are the current focus for clinicians[4,5].In this study, patients with malignant tumors in the head and neck were given Lanzhou Formula with Bingpeng Powder mouthwash for gargling during radiotherapy, so that its prevention and treatment effects could be explored. The report is as follows.

MATERIALS AND METHODS

General Information

A total of 200 patients with head and neck malignant tumors who received radiotherapy in our hospital from April 2018 to April 2020 were selected as research objects, and they were randomly divided into the study group and the control group. In the study group, there were 55 males and 45 females,with an average age of (41.5±28.5). Clinical staging showed 4 cases of stage I, 6 cases of stage II, 70 cases of stage III, and 20 cases of stage IV. In the control group, there were 58 males and 42 females,with an average age of (40.5±29.5). The clinical staging showed 4 cases of stage I, 6 cases of stage II, 71 cases of stage III, and 19 cases of stage IV.Inclusion criteria: (1) The patients were diagnosed as malignant tumors in the head and neck by pathological diagnosis. (2) The general condition was good, and the KPS score was60 points. (3) The patients was 18-70 years old. (4) Both groups were informed and agreed to join this study. Exclusion criteria: (1) The patients with severe internal medicine diseases and severe infections. (2) The patients has primary tumors other than head and neck malignant tumors. (3)Patients allergic to the drugs used in this study.

Methods

Both groups received the same radiotherapy:the total radiation dose given to the primary lesion area was 66-69.96 Gy, 2.0-2.12 Gy/time. Positive lymph nodes identified by imaging tests were given 2.0 Gy/time, with a total dose of 66 Gy. Preventive exposure areas were given 1.6-2.0 Gy/time, with a total dose of 46-50 Gy. 5 times/week, and 33 times in total.

Both groups used mouthwash to prevent and treat radiation-induced oral mucositis from the first day of the radiotherapy to the end of the radiotherapy.Specific drugs and doses of the mouthwash for the control group: 500 mL of normal saline,125 mg of vitamin B12, 400 000 U of gentamicin, and 1 g of lidocaine, prepared by aseptic operation at room temperature. The study group used Lanzhou Formula with Bingpeng Powder mouthwash for gargling. Its specific drugs and doses:Natrii Sulfas Exsiccatus15 g, finely groundBorax9 g andBorneolum Syntheticum1 g (Bingpeng Powder),Radix Salviae Miltiorrhizae30 g,Fructus Corni30 g,Radix Platycodonis20 g,Radix Ophiopogonis20 g,Radix Scrophulariae15 g,Radix Glycyrrhizae15 g,Herba Scutellariae Barbatae15 g,Radix Glehniae15 g,Radix Codonopsis15 g,Radix Rehmanniae Recens15 g, fibrous roots ofRadix Ginseng15 g,Herba Hedyotis15 g, andFructus Schisandrae Chinensi10 g. They were decocted with water to 500 mL, and the prepared Bingpeng Powder was added, with honey 100 g. It was used as the mouthwash after shaking well. The gargle was used before and after each meal (6 times/day), before and after the radiotherapy (2 times/day), and before and after sleeping (2 times/day), with a total of 10 times/day, 5 mL/time, and gargling about 5 min/time.When gargling, the patient needed to swing the head from side to side and back and forth, and blow the cheek for the mouthwash to cover the entire mouth to enhance the efficacy. The efficacy in the 2 groups was observed at the end of the radiotherapy.

Observation Indicators

Occurrence of radiation-induced oral mucositis

Occurrence of radiation-induced oral mucositis in the 2 groups was assessed and recorded, using the acute radiation-induced injury grading standard established by Radiation Therapy Oncology Group(RTOG). Grade 0 means no significant changes in the oral mucosa. Grade 1 means congestion in the oral mucosa, with or without mild pain, which can be relieved without treatment. Grade 2 means lamellar mucositis, or accompanied by inflammatory secretions and moderate pain, which needs to be relieved with analgesics. Grade 3 means fused fibrous mucositis, with severe pain, which requires anesthesia to get relieved. Grade 4 means the patient has oral ulcers, bleeding, oral mucosal necrosis, etc.

Chewing and swallowing functions

Chewing and swallowing functions in the 2 groups were compared. The scoring standard: 1 point (normal), 2 points (only soft food), 3 points(only liquid food), and 4 points (not eating any food).

KPS Scores

The KPS score table was used to determine physical status in the 2 groups before and after the treatment. The total score was 0-100 points. The higher the score, the better the physical status. 100 points means normal, no symptoms and signs; 90 points means able to perform normal activities with mild symptoms and signs; 80 points means barely performing normal activities, with some symptoms or signs; 70 points means able to take care of themselves, but unable to maintain normal life and work; 60 points means can take care of most of their lives, but occasionally need help from others; 50 points means often need someone to take care of 40 points means can not take care of themselves, need special care and help; 30 points means seriously unable to take care of themselves; 20 points means serious illness, need for hospitalization and active supportive treatment; 10 points means critical illness, imminent death; 0 points means death.

Statistical Methods

SPSS 19.0 was applied for analysis, with the χ2test for enumeration data (%), andttest for measurement data ().P＜0.05 indicates a significant difference.

RESULTS

Comparison on the Occurrence of Radiationinduced Oral Mucositis Between the 2 Groups

At the end of the radiotherapy, there was no Grade 4 radiation-induced oral mucositis in the 2 groups. Compared with the control group, the radiation-induced oral mucositis in the study group basically belonged to Grade 1 and Grade 2, with a lower incidence of Grade 3 (P＜0.05). The statistical results are shown in Table 1.

Comparison on Chewing and Swallowing Functions between the 2 Groups

At the end of the radiotherapy, the chewingand swallowing functions in the 2 groups were decreased, but patients with 2 points chewing and swallowing functions in the study group were more than those in the control group, and patients with the 3 points were less than those in the control group(P＜0.05). The details are shown in Table 2.

Table 1. Comparison on the Occurrence of Radiation-induced Oral Mucositis between the 2 Groups [n (%)]

Table 2. Comparison on Chewing and Swallowing Functions between the 2 Groups [n (%)]

Comparison on KPS Scores Between the 2 Groups

At the end of the radiotherapy, the KPS scores were decreased, but those in the study group were higher than those in the control group (P＜0.05). The details are shown in Table 3.

Table 3. Comparison on KPS Scores between the 2 Groups , Point)

Table 3. Comparison on KPS Scores between the 2 Groups , Point)

Group Cases KPS score before the treatment after the treatment Control group 100 67.7±8.2 36.7±5.1 Study group 100 68.0±9.4 48.6±3.8 t value 1.509 12.614 P value ＞0.05 ＜0.05

DISCUSSION

Radiation-induced oral mucositis is a common complication that occurs during radiotherapy for patients with malignant tumors in the head and neck. Most of them are dose-limiting toxic reactions,and the symptoms will slowly recover with the end of radiotherapy[6]. But for those with severe symptoms,it is fatal and harmful, and active and effective prevention and treatment measures are required[7].Radiation-induced oral mucositis can be prevented under certain circumstances, among which nursing intervention and good oral hygiene are the main preventive measures, and the treatment is mainly to reduce complications and relieve the patient's clinical symptoms, such as pain control, nutritional support, infection prevention, etc.[8,9]. This study showed that at the end of the radiotherapy, there was no Grade 4 radiation-induced oral mucositis in the 2 groups. It basically belonged to Grade 1 and Grade 2, with a lower incidence of Grade 3.Compared with the control group, the incidences of Grade 1 and Grade 2 radiation-induced oral mucositis in the study group were higher than those in the control group (P＜0.05), while the incidence of Grade 3 radiation-induced oral mucositis was lower than that in the control group (P＜0.05). At the end of the radiotherapy, the chewing and swallowing functions in the 2 groups were decreased, but patients with 2 points chewing and swallowing functions in the study group were more than those in the control group (P＜0.05), and patients with the 3 points were less than those in the control group (P＜0.05). At the end of the radiotherapy, the KPS scores were decreased, but the KPS scores in the study group were higher than those in the control group (P＜0.05). It shows that in the course of radiotherapy for patients with malignant tumors in the head and neck, simultaneously using the Chinese materia medica mouthwash that consists of Lanzhou Formula with Bingpeng Powder can decrease the severity of oral mucositis, protect the patient's chewing and swallowing functions, and reduce the impact of radiotherapy on the patient's physical status, thereby improving the quality of life of the patient. Modified "Lanzhou Formule with Bingpeng Powder" is a special prescription for preventing and treating radiation-induced oral mucositis, which was formulated by Professor PEI Zheng-xue, a well-known expert in integrated traditional Chinese and western medicine. It is mainly made up of Liuwei Dihuang Decoction (六味地黄汤), Shengmai Powder (生脉散) and Bingpeng Powder. Professor PEI Zheng-xue believes that radioactive rays belong to a fire-heat toxin in traditional Chinese medicine. It invades the human body and causes excessive heat toxins in the body,which is very easy to injure fluid and Qi (气), and also damage the body's collaterals. Therefore,Professor PEI Zheng-xue advocates that excessive heat toxins, Qi-Yin (阴) deficiency and stasis of collaterals are the main etiology and pathogenesis of radiation-induced oral mucositis, and the main principles of treatment for radiation-induced oral mucositis are clearing heat-fire and detoxification,replenishing Qi and nourishing Yin to promote fluid,as well as promoting blood circulation to remove blood stasis and relieve pain[10]. However, the kidney is the congenital foundation and a water-Zang(水脏), which governs body fluids. The spleen is the acquired foundation, and the spleen and stomach are origin of producing Qi and blood. Fluid and blood are from the same source. Therefore, invigorating spleen and supplementing kidney lead to sufficient Qi and blood as well as body fluids. The the oropharynx, skin and mucosas can be moisturized,which is the root of treatment for injured healthy Qi(正气) of the human body caused by radioactive rays. Supplementing kidney can significantly improve the hematopoietic system, endocrine system and specific immune system of the human body. while invigorating spleen is mainly used for improving the autonomic nervous system and nonspecific immune system[11,12]. The basic strategy of the modified "Lanzhou Formula with Bingpeng Powder" is benefiting Qi and Yin, invigorating spleen and kidney, as well as clearing heat and removing toxicity. The prescription takes the "three tonics"of Liuwei Dihuang Decoction, and abandons its"three purges", aiming at focusing on nourishing Yin and supplementing kidney.Radix Rehmanniae Preparatain the prescription is replaced withRadix Rehmanniae Recens, which can clear heat with bitter-cold, and nourish Yin with sweet-cold and texture of moisture. It is a cooling and nourishing ingredient, and is good at nourishing Yin, clearing heat and cooling blood.Fructus Cornihas the function of nourishing liver and kidney. The general dose is 6-12 g, but the dose in this prescription was increased to 30 g, which means "kidney governing bone, the bone generating marrow, and the marrow and blood being homologous". Modern medical experimental studies have proved that high-doseFructus Cornican improve bone marrow hematopoietic function. In addition, fluid and blood are homologous and belong to Yin fluid of the human body. The two physiologically transform and interact with each other, and participate in regulation of body fluids. Therefore, supplementing blood can also produce fluid.Rhizoma Dioscoreaeis sweet in flavor with a neutral property. It enters the Lung,Spleen and Kidney channels, and has functions of nourishing spleen and stomach, producing fluid and benefiting lung, and nourishing kidney and astringing essence. Shengmai Powder is a famous prescription in ancient times, which benefits Qi and nourishes Yin.Radix Glehniae, fibrous roots ofRadix GinsengandFructus Schisandrae Chinensisinvigorate spleen and benefit Qi, as well as nourish Yin and produce fluid.Herba Hedyotis,Herba Scutellariae Barbatae,Radix Glycyrrhizae,Borneolum Syntheticum,Borax,Natrii Sulfas Exsiccatus, etc.can clear heat, remove swelling, astringe sores and promote granulation. Radix Salviae Miltiorrhizae promotes blood circulation and remove blood stasis.The whole prescription has the power of invigorating spleen and kidney, benefiting Qi and nourishing Yin, clearing heat and removing toxicity, as well as promoting blood circulation and removing blood stasis, which can alleviate clinical symptoms and improve the patient's quality of life.

In summary, during radiotherapy for patients with malignant tumors in the head and neck, gargling with Lanzhou Formula with Bingpeng Powder mouthwash can reduce the severity of radiationinduced oral mucositis, protect the patient's chewing and swallowing functions to a certain extent,improve the patient's physical status, and improve the patient's quality of life. It is worthy of clinical application and promotion.