Efficacy and Safety of Qibei Jiedu Formula Versus Placebo in Preventing and Managing Acute Radiation Dermatitis in Breast Cancer Patients: A Prospective, Double-blind, Randomized Controlled Trial
Phase: NA
Conditions: Acute Radiation Dermatitis, Traditional Chinese Medicine (TCM), Breast Cancer
Sponsor: LI FENG

Efficacy and Safety of Qibei Jiedu Formula Versus
Placebo in Preventing and Managing Acute
Radiation Dermatitis in Breast Cancer Patients: A
Prospective, Double-blind, Randomized
Controlled Trial
Research institution: National Cancer
Center/Cancer Hospital, Chinese Academy of
Medical Sciences and Peking Union Medical
College
Project Leader: Feng Li
Version date: 2025-10-20
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NCT Number: NCT ID not yet assigned

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I. Research Background and Objectives
1.1 Research Background
As the most prevalent malignant tumor among women globally, breast cancer is showing a
continuous increase in disease burden [1]. The latest epidemiological data from the China National
Cancer Center in 2024 indicate that the standardized incidence rate of breast cancer in China has
reached 40 per 100,000, ranking first among female malignant tumors, with the onset age being
approximately 10 years earlier than in Western countries, demonstrating a significant trend toward
younger patients [2]. This disease not only severely threatens patients 'lives and health but also
imposes a heavy dual burden on patients' families and the social healthcare system due to its long
treatment cycle and high costs. Modern breast cancer treatment has established a comprehensive
therapeutic model based on surgery, combined with radiotherapy, chemotherapy, endocrine
therapy, and targeted therapy through multidisciplinary collaboration. Among these, radiotherapy
serves as a key means for local control, with approximately 70% of breast cancer patients
requiring radiotherapy intervention.Extensive clinical evidence has demonstrated that standardized
radiotherapy can significantly reduce the local recurrence rate and improve the 5-year survival rate
to over 85% [3]. However, while radiation effectively kills tumor cells, it inevitably causes
damage to normal tissues, leading to treatment-related toxicities that pose a major clinical
challenge.
Acute radiation dermatitis, as the most common adverse reaction of radiotherapy, is
pathologically characterized by an inflammatory cascade reaction in skin tissues induced by
ionizing radiation. Clinical data indicate that over 95% of breast cancer patients undergoing
radiotherapy experience varying degrees of skin damage, manifested as progressively worsening
erythema, edema, and desquamation [4].According to the CTCAE grading criteria, grade 1-2
dermatitis may cause patients discomfort such as pruritus and burning pain, significantly affecting
quality of life. Severe dermatitis of grade 3 or higher may lead to secondary complications such as
skin ulcers and bacterial infections, forcing approximately 15-20% of patients to adjust their
radiotherapy regimens, which directly impacts tumor control efficacy [5]. The prevention and
management of these complications have become critical clinical challenges in the field of breast
cancer radiotherapy.
The pathogenesis of acute radiation dermatitis involves multifactorial interactions, with a

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complex pathophysiological process. At the molecular level, ionizing radiation directly damages
the DNA structure of basal cells and hair follicle cells in the skin, leading to programmed cell
death through activation of the p53-dependent apoptosis pathway. Concurrently, radiation disrupts
the dermal microvascular system, causing endothelial cell injury and increased capillary
permeability, which results in local tissue ischemia and hypoxia. This subsequently triggers the
activation of inflammatory signaling pathways such as NF-κB, promoting the massive release of
pro-inflammatory factors like IL-6, thereby inducing a sustained inflammatory response [6,7].
Clinical practice has demonstrated that the risk of radiation dermatitis is closely associated with
multiple critical factors. In terms of treatment, the total radiation dose (particularly>40Gy)
significantly increases the risk, influenced by factors such as fractionated dose, irradiation field
size, and radiotherapy techniques. On the patient side, elderly individuals are more prone to
impaired skin repair capacity, and comorbidities such as diabetes mellitus also elevate the
incidence and severity of acute radiation dermatitis [6,8]. Currently, clinical management of acute
radiation dermatitis remains challenging. Conventional treatments primarily employ symptomatic
strategies, including topical corticosteroids to suppress inflammatory responses, antibiotic
ointments to prevent secondary infections, and hyaluronic acid-containing moisturizers to repair
the skin barrier. However, these methods have significant limitations: long-term use of
glucocorticoids may lead to adverse effects such as skin atrophy and telangiectasia; antibiotic
misuse can cause dysbiosis and drug resistance; and simple moisturization therapy often fails to
interrupt the inflammatory cascade [8]. In recent years, with a deeper understanding of the
molecular mechanisms of radiation dermatitis, novel therapeutic strategies have emerged.
Recombinant human epidermal growth factor (rhEGF) can accelerate wound healing by
promoting keratinocyte proliferation [9]; low-intensity laser therapy (LLLT) can modulate local
immune function and reduce inflammatory responses [10]; mesenchymal stem cell exosomes have
also demonstrated promising tissue repair potential [11]. However, these innovative therapies are
still largely in clinical trial stages, and issues such as efficacy stability, treatment costs, and
long-term safety require further validation. This situation highlights the urgent need to develop
safer and more effective prevention and treatment strategies.
Traditional Chinese Medicine (TCM) has extensive experience and unique advantages in

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treating radiation dermatitis. TCM posits that the occurrence of acute radiation dermatitis can be
classified under the categories of "drug toxicity" and "drug eruption" [12,13]. The core
pathogenesis is "deficiency of both qi and yin, with mutual accumulation of stasis and toxicity."
Treatment should focus on replenishing qi and nourishing yin, dispelling wind and activating
blood circulation, as well as detoxifying and resolving turbidity. The Qibei Jiedu Formula is a
compound herbal formula based on the TCM theory of "strengthening the body's defenses,
removing stasis, and detoxifying." Its main components include Astragalus membranaceus,
Rehmannia glutinosa, Hedyotis diffusa, Gleditsia sinensis, Euphorbia hirta, Lithospermum
erythrorhizon, Tribulus terrestris, stir-fried Shenqu, and raw licorice. The herbal formula is
composed of Astragalus membranaceus as the principal herb, which tonifies qi, strengthens
defensive qi, and supports toxin elimination to promote tissue regeneration; Rehmannia glutinosa
for cooling blood and promoting fluid production; Hedyotis diffusa for detoxification and abscess
resolution; Gleditsia sinensis for wound healing and turbid fluid resolution; and Cynanchum
wilfordii for wind-dispelling, collaterals dredging, and dysentery relief, collectively serving as
ministerial herbs. Lithospermum erythrorhizon assists Rehmannia glutinosa and Hedyotis diffusa
in cooling blood and detoxification, while Tribulus terrestris supports Gleditsia sinensis and
Cynanchum wilfordii in liver regulation, wind-dispelling, and rash resolution. Fried Shenqu
(Saccharomyces cerevisiae) aids digestion and harmonizes the stomach, while serving as a
counterbalance to prevent cold-induced stomach injury. Glycyrrhiza uralensis acts as the
messenger herb, tonifying qi, detoxifying, and harmonizing the other herbs. Preliminary clinical
observations and small-sample studies suggest that the Astragalus and Tribulus Detoxification
Formula demonstrates significant clinical value in treating moderate-to-severe acute radiation
dermatitis through synergistic effects of toxin support and tissue regeneration, dampness
absorption and wound healing, and blood-activating and wind-dispelling. This formula not only
effectively alleviates acute symptoms such as skin erythema, exudation, and pain but also
promotes the repair and regeneration of damaged skin, significantly improving patients' quality of
life. Therefore, our research team plans to initiate a small-scale exploratory clinical trial, primarily
aiming to provide preliminary efficacy and safety data for subsequent large-scale clinical studies.
The results will guide the estimation of effect sizes and hypothesis generation for future trials,
laying the foundation for rigorous large-sample, multicenter randomized controlled clinical trials

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to scientifically evaluate the efficacy, dose-response relationship, and long-term safety of this
formula, thereby providing higher-level evidence-based medicine for its clinical application.
1.2 Research Objective
1.2.1 Evaluate the preventive and therapeutic effects of Qibei Jiedu Formula on acute
radiation dermatitis in breast cancer patients, including the incidence of grade 2 or higher radiation
dermatitis, wound healing time, and symptom relief.
1.2.2 Observation of the safety of Qibei Jiedu Formula.
1.2.3 Investigate the potential role of Qibei Jiedu Formula in improving patients' quality of
life.
1.2.4 Exploring the potential mechanisms of Qibei Jiedu Decoction in the prevention and
treatment of acute radiation dermatitis in breast cancer patients (through exploratory indicators
such as inflammatory factors and skin microbiota).
1.2.5 This study is a small-scale exploratory clinical trial designed to obtain preliminary
efficacy and safety data from 60 subjects, evaluating the "loading effect" of Qibei Jiedu Formula
on "standard basic treatment". It aims to provide effect size estimation and hypothesis generation
basis for subsequent large-scale studies, rather than to draw confirmatory conclusions.
II. Research Protocol
2.1 Case Source
A total of 60 breast cancer patients who met the inclusion and exclusion criteria and were
admitted to the radiotherapy ward of the Cancer Hospital of the Chinese Academy of Medical
Sciences from October 2025 to December 2026 were enrolled in the study.
2.2 Diagnostic Criteria
2.2.1 Western Medical Diagnostic Criteria
①Diagnostic criteria for breast cancer: Refer to the "CSCO Guidelines for the Diagnosis
and Treatment of Breast Cancer" (2024 edition) [14].
②Radiation dermatitis: According to the grading criteria of the Common Toxicity Criteria for
Adverse Events (CTCAE 5.0) in the United States, the radiation dermatitis in this study was
classified as follows:
Table 1 CTCAE 5.0 Grading Criteria for Radiodermatitis

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classify
clinical manifestation
Level 1
Mild erythema or dry desquamation
Level 2
Moderate to severe erythema; patchy moist desquamation, mostly localized to
wrinkles and folds; moderate edema
Level 3
Wet desquamation is not limited to wrinkles and folds; it may also result from
minor injuries or friction-induced bleeding.
Level 4
Life-threatening; skin necrosis or true-layer ulceration; bleeding from the affected
area; requires skin grafting
2.2.2 Traditional Chinese Medicine Diagnostic Criteria
The TCM syndrome scale was developed with reference to the Clinical Research Guidelines
for New Traditional Chinese Medicine Drugs (2002 Edition) [15], the Diagnosis and Treatment
Guidelines for Malignant Tumors in Traditional Chinese Medicine [16], and Traditional Chinese
Medicine Surgery [17].
Based on the patient's symptoms, when two of the two primary symptoms listed in the table
are present, or one primary symptom accompanied by two secondary symptoms, and both primary
and secondary symptoms simultaneously meet any of the following conditions, the syndrome can
be diagnosed as "Qi-Yin Deficiency with Stasis-Toxin Interconnection Syndrome":
①Main symptoms: fatigue, chest tightness and shortness of breath, heat in the palms, soles and
chest, dry mouth and throat; Main symptoms: localized pain, skin and nails
①Main symptoms: fatigue, chest tightness and shortness of breath, heat in the palms, soles and
chest, dry mouth and throat; Secondary symptoms: dark lips, nails and complexion, subcutaneous
ecchymosis
②Main symptoms: localized pain, skin and nail disorders + secondary symptoms; fever with
sweating, irritability and insomnia, scanty dark urine, dry and hard stools
Table 2 Scale for Syndrome of Deficiency of Both Qi and Yin with Mutual Combination of Stasis
and Toxin
Quantitative Scoring Table for TCM Syndrome Classification
symptom
None (0
point)
Mild (2
points)
Moderate (4
points)
Severe (6 points)
cardinal
symptom
exhaustion
not have
exertion leads
to exhaustion
exertion leads to
exhaustion
No movement,
no fatigue
chest tightness
not have
Shortness of
Shortness of
No movement,

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and shortness of
breath
breath after
activity
breath with
slight movement
no shortness
dysphoria
in
chestpalms-soles
not have
palmar and
plantar
hyperthermia
Exposure of
limbs beyond
clothing
coldness in hands
and feet relieved
by grasping cold
objects
dry mouth and
throat
not have
light
Drinking water
can alleviate the
symptoms.
drinking without
relieving
localized pain
not have
Occasional
occurrence,
may resolve
spontaneously
within 30
minutes
The pain
duration is less
than 3 hours per
day, and
tenderness is
pronounced
upon palpation.
persistent pain,
severe pain
squamous and
dry skin
not have
rough and dry
skin
rough, dry skin
with darkening
of color
rough, dry skin
with darkening of
skin color,
accompanied by
subcutaneous
ecchymoses and
petechiae
symptom
None (0
point)
Mild (1
point)
Moderate (2
points)
Severe (3 points)
minor
symptom
febrile sweating
not have
Occasionally
Recurrent chest
and back heat
flashes
Generalized hot
flashes, profuse
sweating,
frequently
occurring
restless sleep
not have
Occasional
irritability
with easy
awakening
during sleep
restless and
difficulty falling
asleep
Restless and
sleepless all night
lip color
not have
dull
coloration of
the lip and
nail
dark purple
coloration of the
lip and nail
dull and
bluish-purple
coloration of the
lip and face
ecchymosis
not have
1 site
2 sites
3 or more sites
oliguria with
reddish urine
not have
yellow urine
yellowish-red
urine with a
sensation of heat
dull and scanty
urine with
yellowish-red
color and burning

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sensation
dry stool
not have
dry stool, one
per day
Constipation,
occurring every
two to three days
difficult
defecation, once
every few days
2.2.3 Drainage Standards
Inclusion criteria:
①Patients with pathologically confirmed unilateral stage I-III non-invasive breast cancer
who have undergone breast-conserving surgery or modified radical mastectomy for breast cancer,
and who have received or plan to receive standard postoperative adjuvant therapy (according to
the latest clinical guidelines);
②Adopt postoperative adjuvant radiotherapy, with the patient scheduled to receive a
high-dose fractionation regimen of 40-50 Gy/15 fractions based on the recommended radiation
target dose from the National Comprehensive Cancer Network (NCCN) Breast Cancer Guidelines
and the CSCO Guidelines for the Diagnosis and Treatment of Breast Cancer (2024 edition).
③Conform to the syndrome of deficiency of both qi and yin with mutual accumulation of
blood stasis and toxins;
④Karnofsky Performance Score (KPS) ≥70 points;
⑤Age ≥18 years, female;
⑥Voluntary participation in the study and signing of the informed consent form.
Exclusion criteria:
①Patients with grade 4 radiation dermatitis present at enrollment or developing during the
study requiring emergency intervention;
②Received radiotherapy to the breast or chest within the past 3 months;
③
Any skin disease or condition that may interfere with the assessment of radiation
dermatitis, such as active infection, atopic dermatitis, psoriasis, vitiligo, active collagen
vascular diseases (e.g., scleroderma, systemic lupus erythematosus), or other autoimmune
diseases known to significantly alter skin appearance or physiological responses;
④Pre-treatment liver or kidney dysfunction of grade 2 or above or hematologic toxicity

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(meeting the CTCAE 5.0 grading criteria):
⑤
Currently participating in other clinical trials or concurrently using other traditional
Chinese medicine preparations;
⑥Unstable mental state, unable to cooperate with the study;
⑦Pregnant and lactating patients;
⑧Patients with known hypersensitivity to any component of the Chinese herbal medicines
used in this study.
2.2.4 Shedding Criteria
①Poor therapeutic efficacy or adverse reactions that the subject cannot tolerate, making it
impossible to continue the trial, and requesting voluntary withdrawal;
②
Occurrence of serious adverse events, or concurrent development of other diseases or
severe complications during the trial.
2.2.5 Exclusion Criteria
①
Poor medication adherence during treatment, with violations of prescribed medication
protocols;
②Patients who did not complete the observation period specified in the protocol or whose
results were affected by incomplete information.
III. Research Content
3.1 Randomization and Blinding
3.1.1 stochastic
A stratified block randomization design was employed, with a 5-member independent
statistical unit (non-research team) from the Cancer Hospital of the Chinese Academy of Medical
Sciences responsible for generating and safeguarding the random sequence. The random sequence
was generated using SAS 9.4 statistical software and stratified by surgical type (breast-conserving
surgery versus modified radical mastectomy). A total of 60 cases were enrolled in this trial, and
the 60 patients were allocated 1:1 to the treatment group and control group (30 cases each) using a
fixed block design (length=4). The random sequence was sealed in a lightproof envelope and,

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along with an emergency unblinding envelope, was entrusted to a 5-member blind management
team composed of representatives from the Department of Traditional Chinese Medicine, Statistics,
and Ethics Committee of the Cancer Hospital of the Chinese Academy of Medical Sciences. The
sequence was stored in a dedicated institutional safe. Prior to unblinding, neither the patients,
researchers, nor outcome assessors were aware of the group assignments.
3.1.2 Blinding
The study employed a double-blind design, strictly adhering to the "three separations"
principle (i.e., independent random sequence generators, clinical implementers, and data
statisticians). The treatment group (Qibei Jiedu Formula) and the control group (simulant) were
identical in appearance, color, odor, and packaging, with random coding assigned for packaging.
Clinical researchers distributed the corresponding coded medications sequentially according to the
enrollment order of participants, while independent outcome assessors were responsible for
evaluating all subjective indicators. Upon completion of the study, the CRF forms were transferred
to statistical personnel for primary unblinding (A/B group analysis), followed by secondary
unblinding (official disclosure of group assignments) after statistical analysis was completed. All
unblinding procedures were meticulously documented and archived, with oversight by the blind
management team.
3.2 Treatment Protocol
3.2.1 Therapeutic Agents
Treatment group: Qibei Jiedu Formula (Composition: Astragalus membranaceus 10g,
Rehmannia glutinosa 10g, Hedyotis diffusa 10g, Gleditsia sinensis 6g, Euphorbia hirta 10g,
Lithospermum erythrorhizon 10g, Tribulus terrestris 10g, Fried Shenqu 10g, Licorice root 5g).
Control group: Placebo, which was identical to the test drug in appearance, dosage form,
weight, color, and odor, with the dosage of traditional Chinese medicine being 5% of the original
formula.
3.2.2 Intervention Measures
This study is a pragmatic randomized controlled trial. All enrolled patients will receive
standard basic treatment formulated by their respective research centers based on current clinical
guidelines and routine practices. On this unified basis, patients will be randomly assigned to one
of the following two groups:

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Treatment group: standard basic treatment + Jibei Jiedu prescription.
Control group: Standard basic treatment + Simulated agent of Jibei Jiedu Decoction (original
dose 5%).
(1) Standard basic treatment
Radiotherapy regimen: High-dose fractionation (40-45 Gy/15 fractions).
Skin care: Refers to the routine protocol adopted by the research center to prevent radiation
dermatitis (including but not limited to various gel dressings, ointments, or creams). This protocol
is determined by the attending physician based on the patient's specific condition and departmental
protocols. The specific drug names, administration methods, dosages, and duration of use must be
recorded in the case report form.
Stability requirements: To ensure research quality, the skin care regimen for patients should
remain as stable as possible after enrollment.
(2) Loading intervention
Subjects began taking Qibei Jiedu Formula or a placebo from the first day of radiotherapy,
with one dose per day. Each dose of decoction was divided into two sachets (100 mL/sachet), with
one sachet taken at each dose. The treatment was administered twice daily (morning and evening)
for three consecutive weeks (21 days, synchronized with radiotherapy).
(3) Rescue Treatment Protocol
When a subject develops grade ≥2 radiation dermatitis (based on CTCAE v5.0 criteria) or
reports intolerable pruritus/pain (numerical rating scale [NRS] ≥4), the predefined standardized
rescue treatment protocol may be initiated. Investigators should select from the following
protocols based on the patient's clinical presentation, with detailed documentation of the initiation
date, termination date, and selected protocol category (A or B). In principle, for patients presenting
with predominant symptoms of moist desquamation and exudation, protocol A (healing-promoting
agents, such as recombinant human epidermal growth factor) should be prioritized. For patients
exhibiting severe erythema, pruritus, or burning pain, protocol B (anti-inflammatory agents, such
as medium-to low-potency topical corticosteroid creams, e.g., hydrocortisone cream or
mometasone furoate cream) should be prioritized.
IV. Outcome Metrics

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4.1 General Situation Survey Form
(1) Age: years, mean ± standard deviation
(2) BMI: kg/m², mean ± standard deviation
(3) Smoking history: n (%)
(4) History of diabetes: n (%)
(5) Menopause status: n (%)
(6) KPS score: n (%)
(7) History of chemotherapy: n (%)
(8) History of connective tissue disease or immune disorder: n (%)
(9) Fitzpatrick classification: n (%)
(10) Type of surgery: n (%)
(11) Radiotherapy techniques (IMRT/VMAT): n (%)
(12) Radiation therapy coverage: n (%)
(13) Adjuvant therapy during the trial: n (%)
(14) Planned CT breast volume: cm³, mean ± standard deviation
(15) Cutaneous Dmax (Gy, mean ± standard deviation)
(16) Skin Dmean (Gy, mean ± standard deviation)
(17) Skin V20Gy (% mean ± SD)
(18) Skin V30Gy (% mean ± SD)
(19) Skin V40Gy (% mean ± SD)
(20) Skin V45Gy (% mean ± SD)
4.2 Efficacy Evaluation
4.2.1 Primary outcome measures: incidence of radiation dermatitis
Definition: The proportion of patients who developed CTCAE grade 2 or higher radiation
dermatitis during radiotherapy and within 1 month after radiotherapy completion, as confirmed by
the investigator.
Assessment method: Incidence = (Number of patients with at least one ≥grade 2 event
recorded / Total number of patients) × 100%.

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radiodermatitis
Level 1
Mild erythema or dry desquamation
Level 2
Moderate to severe erythema; patchy moist desquamation, mostly localized to
wrinkles and folds; moderate edema
Level 3
Wet desquamation is not limited to wrinkles and folds; it may also result from
minor injuries or friction-induced bleeding.
Level 4
Life-threatening; skin necrosis or true-layer ulceration; bleeding from the affected
area; requires skin grafting
Level 5
die
4.2.2 Secondary Outcomes
(1) Median time to first occurrence of radiation dermatitis: the time required for the
investigator to confirm the first occurrence of radiation dermatitis meeting CTCAE 5.0 Level 2
criteria.
(2) Median time to wound healing in skin
Definition: The skin wound healing time refers to the duration from the onset of grade 2-3
radiation dermatitis to complete wound healing. According to the CTCAE 5.0 and the "Guidelines
for Clinical Research of New Traditional Chinese Medicine Drugs," the grading of radiation
dermatitis is evaluated, and the skin wound healing time is defined as the period from the
investigator's confirmation and initial recording of ≥grade 2 to recovery to <grade 2 (i.e., grade 0
or 1) [18,19].
(3) Radioactive Dermatitis Symptom Rating Scale (RISRAS):
RISRAS (Total score 0-36)
Researcher section (total score 0-24)
spiloplaxia
0□
Normal skin
1□
light pink
2□
kermesinus
3□
bright red
4□
royal purple
dry
desquamation
0□
Normal skin
1□
＜25%
2□
25-50%
3□
50-75%
4□
＞75%
wet
desquamation
0□
1.5□
3.0□
4.5□
6□

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Normal skin
＜25%
25-50%
50-75%
＞75%
necrosis
0□
Normal skin
2.5□
＜25%
5.0□
25-50%
7.5□
50-75%
10□
＞75%
remarks
Dry desquamation, wet desquamation, and necrosis were assessed based on the
proportion of the irradiated field area affected by dermatitis.
Patient section (total score 0-12)
symptom
in no shape
appreciably
somewhat
very serious
Is there any pain, discomfort,
or sensitivity in the treated
area?
0□
1□
2□
3□
Is the skin in the treatment
area itchy?
0□
1□
2□
3□
Is there a burning sensation in
the treated area?
0□
1□
2□
3□
To what extent do your skin
reactions and symptoms affect
your daily life?
0□
1□
2□
3□
(4) Quality of Life Assessment
a. Breast Cancer-Specific Questionnaire (EORTC QLQ-BR23)
1 point means none, 2 points mean a little, 3 points mean some, and 4 points mean a lot
Over the past week (past 7 days)
1. Why are you thirsty?
□1
□2
□3
□4
2. Do you notice any unusual taste in your food or drinks?
□1
□2
□3
□4
3. Do you experience eye pain, stinging, or tearing?
□1
□2
□3
□4
4. Do you experience hair loss?
□1
□2
□3
□4
5. You must answer this question if you experience hair
loss: Do you feel distressed by hair loss?
□1
□2
□3
□4
6. Do you feel unwell or physically uncomfortable?
□1
□2
□3
□4

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7. Do you experience hot flashes?
□1
□2
□3
□4
8. Do you have a headache?
□1
□2
□3
□4
9. Do you feel that your physical appearance has become
less attractive due to your illness or treatment?
□1
□2
□3
□4
10. Do you feel that your illness or treatment has
diminished your femininity?
□1
□2
□3
□4
11. Do you find it uncomfortable to watch yourself naked?
□1
□2
□3
□4
12. Are you dissatisfied with your body appearance?
□1
□2
□3
□4
13. Are you concerned about your future health?
□1
□2
□3
□4
Over the past four weeks (28 days)
14. How interested are you in sex?
□1
□2
□3
□4
15. How active is your sexual life? (Have you had sexual
intercourse or not?)
□1
□2
□3
□4
16. You only need to answer this question if you have had
sexual intercourse in the past four weeks: How do you feel
about the pleasure of sexual intercourse?
□1
□2
□3
□4
In the past week (past 7 days)
17. Do you experience pain in your arm or shoulder?
□1
□2
□3
□4
18. Do you have swelling in your arm or hand?
□1
□2
□3
□4
19. Do you have difficulty raising or extending your arm?
□1
□2
□3
□4
20. Is there pain in the affected breast area?
□1
□2
□3
□4
21. Is there swelling in the affected breast area?
□1
□2
□3
□4
22. Is the affected breast area hypersensitive?
□1
□2
□3
□4
23. Are there any dermatological issues (e.g., pruritus,
xerosis, desquamation) in the affected breast area? This
□1
□2
□3
□4

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alteration involves more than one-quarter of the mammary
gland tissue.
b.Dermatology Quality of Life Index Questionnaire (DLQI)
Dermatology Quality of Life Index Scale
Very
serious
serious
light
not
have
1. Have you experienced severe pruritus or pain
symptoms on your skin during the past week?
□3
□2
□1
□0
2. Over the past week, how many times have your skin
lesions made you aware of or experienced feelings of
"embarrassment,"
"frustration," or "sadness"?
□3
□2
□1
□0
3. To what extent have your skin lesions affected your
shopping, household chores, or gardening activities
over the past week?
□3
□2
□1
□0
4. Have you chosen different or special clothing or
shoes due to skin discomfort in the past week?
□3
□2
□1
□0
5. To what extent have your skin lesions affected your
social or recreational activities during the past week?
□3
□2
□1
□0
6. To what extent has your skin lesion affected your
ability to engage in physical activities over the past
week?
□3
□2
□1
□0
7. Have your skin lesions interfered with work or study
in the past week? □No □Yes
If yes: How much do your skin problems affect your
work or study?
□3
□2
□1
□0
8. To what extent have your skin lesions caused distress
to your companions, close friends, or family members
over the past week?
□3
□2
□1
□0

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9. To what extent have your skin lesions caused
difficulties in sexual intercourse during the past week?
□3
□2
□1
□0
10. Does your skin condition cause inconvenience in
daily life?
□3
□2
□1
□0
(5) Skin Reflection Spectrophotometry (SRS) measurement:
During each follow-up visit and on the day of the end of the traditional Chinese medicine
(TCM) treatment course, the measurement instrument was a colorimeter (CR-10 Plus, Konica
Minolta, Tokyo, Japan). This device has been validated for non-invasive and objective assessment
of radiation dermatitis (RD). Measurements were taken three times at different random locations
in each quadrant of both breasts (a total of 4 quadrants), with the mean value used to minimize
error. The CIE L*a*b* standard chromaticity system was employed: L*: brightness value (0–100),
where lower values indicate deeper skin pigmentation. a*: red-green axis value, with higher
positive values suggesting more pronounced erythema (RD). b*: yellow-blue axis value, which
serves as a secondary indicator in the evaluation of acute radiation dermatitis [20 – 22]. The
changes in chromaticity values of the affected skin from baseline at different time points (ΔL*, Δ
a*, Δb*) were statistically analyzed. Measurements were only taken at the beginning of the study
(baseline) and at the end of radiotherapy (day 21) on the unaffected skin to exclude the influence
of significant systemic skin changes on the trial results.
(6) TCM syndrome scoring (Qi-Yin deficiency and blood stasis-toxin intermingling
syndrome): A TCM syndrome scoring scale was established based on the "Guidelines for Clinical
Research of New Traditional Chinese Medicine Drugs" (2002 edition), "Diagnosis and Treatment
Guidelines for Malignant Tumors in Traditional Chinese Medicine," and "Traditional Chinese
Medicine Surgery." The therapeutic efficacy was evaluated by analyzing the changes in syndrome
scores at different treatment stages, as detailed in Table 2.
The therapeutic efficacy was evaluated using the Traditional Chinese Medicine (TCM)
syndrome score improvement rate method (syndrome score improvement rate = (difference in
scores before and after treatment / pre-treatment score) × 100%). The results were classified into
four grades: complete cure (syndrome score reduction rate ≥95%), marked efficacy (70% ≤

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syndrome score reduction rate <95%), effective (30% ≤syndrome score reduction rate <70%),
and ineffective (syndrome score reduction rate <30%).
The total effective rate = [(Number of cured + effective + significantly effective cases) / Total
number of cases] × 100%.
4.2.3 Exploratory Indicators
（1）Inflammatory markers (TNF- α, IL-6, IL-10, IL-8, etc.): Collect 5 mL of blood from the
median cubital vein of the patient, store in a separation rubber tube (yellow cap), and determine
the inflammatory levels using enzyme-linked immunosorbent assay (ELISA). (Is covered by
medical insurance?)
（2）Skin microbiota analysis: Using sterile cotton swabs, wipe the 5cm×5cm skin surface along
the center and periphery of the irradiation field (with a 2cm non-irradiated area at the edge as
control). Divide the target area into four rectangular zones from top to bottom, maintaining
moderate contact between the swab tip and skin. Perform at least five reciprocating swabs per
zone. After completing one zone, rotate the swab 90 degrees before proceeding to the next zone to
ensure adequate microbial sample coverage. Immediately store the swabs in preservation solution
and conduct skin microbiota analysis using 16S rRNA gene sequencing technology.
（3）Lymphocyte subpopulation analysis: Collect 5 mL of blood from the median cubital vein of
the patient and store it in an EDTA anticoagulant tube (purple cap). Perform flow cytometry to
detect the distribution of lymphocyte subpopulations in peripheral blood.
4.3 Safety Evaluation
(1) Laboratory tests: This study will evaluate laboratory test indicators of all subjects using
the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE)
version 5.0. Laboratory abnormalities meeting any of the following criteria will be defined as
"clinically significant abnormalities" and recorded, tracked, and managed as adverse events:
a) Non-hematologic abnormalities meeting CTCAE 5.0 Level 2 or higher (e.g., hepatic or renal
dysfunction);
b) Hematologic abnormalities meeting CTCAE 5.0 grade 3 or higher (e.g., neutropenia,
thrombocytopenia);

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c) Any laboratory abnormalities that necessitated discontinuation of the study intervention, dose
adjustment, or targeted medical interventions (e.g., leukocyte-elevating agents, hepatoprotective
agents, etc.), regardless of their CTCAE classification.
(2) Adverse Events (AEs) and Adverse Drug Reactions (ADRs): Throughout the trial period,
all adverse events/adverse drug reactions will be closely monitored and recorded. Particular
attention will be paid to their nature, severity, timing, duration, relevance to the investigational
drug (using a 5-level association evaluation: definite, very likely, probable, probably unrelated,
unrelated), management measures, and outcomes. This study will conduct a pooled analysis of the
overall incidence of adverse events/adverse drug reactions, with special reporting on the incidence
of grade ≥3 adverse events and cases leading to study withdrawal.
V. Trial Protocol and Follow-up Plan
All randomized patient visit evaluation time points are shown in Table 5.
Table 5 Visit Flowchart
step
period
Filter
period
stage of therapy
follow-up period
study follow-up
Visit 0
Visit
1
Visit
2
Visit
3
Visit 4
Visit 5
Key Event
Record after
Discharge
Follow-u
p 1
Study date (days)
-7 to 0
days
7±2
days
10±
2
days
14±
2
days
17±2
days
21±2 days
22 to 47 days
49±3
days
1
Sign the informed consent form
√
2
Brief Summary of the Subject's Medical
Record
√
3
Inclusion and Exclusion Criteria
√
4 Clinical and
Safety
Evaluation
Vital signs/Electrocardiogram (ECG)
√
Complete blood count/Liver and kidney
function tests
√
√
√
Drug dispensing
√
Drug recovery
√
6 Skin and
End-point
Radiation Dermatitis Grading/RISRAS Score
√（base
line ）
√
√
√
√
√
(Based on weekly
card evaluations)
√

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VI. Statistical Analysis
6.1 Follow-up
Primary follow-up is conducted in the hospital, supplemented by telephone or WeChat
follow-ups.
6.2 Statistical Methods
SPSS 29.0 software was used, with a significance level set at p<0.05 (two-tailed). All
analyses adhered to the intention-to-treat (ITT) principle. For quantitative data, normally
distributed values were expressed as mean ± standard deviation, while non-normally distributed
values were expressed as median (interquartile range); categorical data were presented as
frequency and percentage. Continuous variables were tested for normality using the Shapiro-Wilk
test, with independent samples t-test applied to normally distributed data and Mann-Whitney U
test to non-normally distributed data. Categorical variables were analyzed using the χ² test or
Indicators
Skin reflection spectrophotometry
√（base
line ）
√
√
√
√
√
√
Symptom Tracking Weekly Card
√
（provide
）
√(Patient
records)
√
（retrie
ve ）
Quality of Life Assessment/Traditional
Chinese Medicine Syndrome Evaluation
√（base
line ）
√
√
√
7 Biological
Sample
Collection
Blood sample (lymphocyte cytokine subsets,
multiplex cytokine assay)
√（base
line ）
√
（postrad
iotherapy
）
Skin swab
√（base
line ）
√
（postrad
iotherapy
）
8
fill in CRF
√
√
√
√
√
√
√
（event-driven
）
√
Shared Page
Concomitant medication
Emergency treatment
adverse event
protocol bias
Review page

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Fisher's exact test (when theoretical frequencies did not meet the
χ ²
test requirements).
Time-event data (e.g., skin healing time, first onset of dermatitis) were estimated using the
Kaplan-Meier method to calculate median time and 95% confidence interval (CI), with intergroup
comparisons performed using the Log-rank test. For primary outcome measures (incidence of ≥
2-grade dermatitis), adjusted hazard ratios were calculated primarily using log-binomial regression
(or Poisson regression with robust standard errors if convergence was not achieved),
supplemented by the χ² test for unadjusted intergroup comparisons. Skin microbiota analysis
employed QIIME2 to assess alpha diversity (intergroup comparisons using Mann-Whitney U test)
and beta diversity (intergroup comparisons using PERMANOVA), with LEfSe analysis used to
identify differential genera.
6.3 Statistical Hypotheses
6.3.1 Primary Outcomes Assumptions
(1) Preventive research:
H₀
(null hypothesis): The incidence of grade ≥2 radiation dermatitis is equal between the
Qibei Detoxification Formula group and the placebo group (P₁
= P₂ ).
H1 (alternative hypothesis): The incidence rates are not equal between the two groups (P1 =
P2).
This study will primarily evaluate the point estimate difference in incidence rates between the
two groups and its 95% confidence interval (CI). The range of the CI will be used to assess
whether there are clinically significant differences, and to provide a basis for sample size
calculation for future Phase III studies.
(2) Therapeutic studies:
H₀ : The survival distributions of wound healing time between the two groups are identical.
H1: The survival distributions of the two groups are different.
This study will primarily evaluate the median healing time difference between the two groups,
along with their 95% confidence intervals (CIs), and the hazard ratio (HR) and its 95% CI.
6.3.2 Secondary Outcomes Hypotheses
For each secondary endpoint (e.g., overall response rate, scale scores, inflammatory markers,

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etc.), similar null hypothesis (H ₀
) and alternative hypothesis (H ₁
) of no difference were
established, with all tests conducted at a two-tailed α=0.05 level.
6.3.3 Description
The statistical analysis in this study will focus on estimating the magnitude of the effect and
its precision, rather than solely on the p-value of hypothesis testing. All preliminary findings will
be utilized to guide the design of subsequent confirmatory studies (e.g., sample size calculation,
selection of primary endpoints).
VII. Ethical Requirements
7.1 Ethics Review and Compliance
This study strictly adheres to the Helsinki Declaration and relevant clinical research laws,
regulations, and standardization protocols of China, and can only be implemented after submission
to the hospital's ethics committee for review and approval. If any revisions to the protocol occur
during the study, they must be resubmitted to the ethics committee for deliberation and approval
before execution. If important new information related to the investigational drug is obtained, the
informed consent form should be promptly revised and resubmitted to the ethics committee for
review and approval before obtaining the informed consent of the subject or their legal guardian
again. All serious adverse events and protocol deviations must be reported to the ethics committee
in a timely manner as required.
7.2 Privacy and Confidentiality Measures
Only authorized personnel of this study (researchers and monitors) may access the medical
records of participants, and all are obligated to maintain confidentiality. The drug regulatory
authority has the right to review clinical trial-related documents. All data processing procedures
are conducted through anonymization, with the removal of information that could directly identify
individuals. Participant medical information is stored at the National Drug Clinical Trial
Institution, ensuring strict information security.
7.3 Informed Consent Procedure
Researchers must fully explain the purpose, nature, expected benefits and potential risks of
the study, alternative treatment options, and the rights and obligations of the subjects under the
Declaration of Helsinki to the subjects or their legal guardians. Only after ensuring that the

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subjects fully understand and voluntarily sign a written informed consent form can they be
enrolled in the study and proceed with the relevant procedures.
7.4 Preservation of Research Data
Researchers must properly preserve all study materials, including subject identification
documents (for cross-referencing with hospital original records), signed informed consent forms,
and all observation record forms. All clinical trial materials should be retained for no less than 5
years after the study concludes.
VIII. Technology Roadmap
VIII. Observation and Analysis of Adverse Events
1. Definition of Adverse Events
Adverse events (AEs) refer to adverse medical events occurring during clinical studies,
regardless of their association with the investigational drug.
2. Observation and Documentation of Adverse Events
Researchers should meticulously observe and document the occurrence time, severity,
duration, measures taken, and outcomes of all adverse events (AEs), and record them in the
Adverse Event Log. For radiation dermatitis, in addition to grading according to the following
general criteria, the severity should primarily be professionally assessed based on the CTCAE
v5.0 standards.
3. Severity Assessment of Adverse Events
Carefully observe the process, severity, management, and outcome of adverse events (AEs)
and record them in the AEs report form. According to the following criteria, the severity of AEs
can be classified as mild, moderate, or severe.
✓Mild: Signs/symptoms are mild, easily tolerated, generally do not affect daily activities,
and do not require special treatment.
✓Moderate: Significant signs/symptoms affecting daily activities, requiring targeted medical
intervention/treatment.
✓Severe: The signs/symptoms are severe, impairing daily activities and requiring active

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medical intervention/treatment.
Note: 'Severe' describes the intensity of the event and is not equivalent to 'serious adverse
event (SAE)'.
4. Determination and Reporting of Serious Adverse Events (SAE)
A serious adverse event refers to any occurrence that poses significant harm to the patient
and/or constitutes a contraindication to continued treatment. In clinical practice, the following
events are included:
✓deadly ；
✓life-threatening ；
✓Requires unplanned hospitalization or prolonged hospital stay;
✓Resulting in permanent or significant disability/loss of function in patients;
✓causes congenital malformations or birth defects;
✓Other significant medical events (not meeting the above criteria but potentially
endangering the subject or requiring medical intervention to prevent the aforementioned
outcomes).
Reporting procedure: Upon the occurrence of a Serious Adverse Event (SAE), the
investigator shall immediately take necessary measures to ensure the safety of the subject and
submit a written 'Subject SAE Report Form' to the institutional ethics committee and other
relevant departments within 24 hours of notification.
5. Outcomes of Adverse Events and Serious Adverse Events (SAEs)
✓die ；
✓Not cured/Not remitted;
✓recure ；
✓Symptoms resolved but sequelae persist;
✓laxation ；
✓not quite clear

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6. Evaluation of the Correlation Between Adverse Events and Medications
(1) Indicators for determining the causal relationship between adverse events and drugs
✓Whether there is a reasonable temporal sequence between the initiation of medication and
the occurrence of adverse events/adverse reactions.
✓
Verify whether the suspected adverse reaction matches any known adverse reaction
profile of the drug.
✓Whether the suspected adverse reaction can be explained by relevant pathological
conditions, concomitant medications, concurrent treatment modalities, or previously administered
therapies.
✓Can the suspected adverse reaction be alleviated or resolved after discontinuation or dose
reduction?
✓Whether the same reaction reoccurs after re-administration of the suspected drug.
According to the above five indicators, the causal relationship is analyzed as positive, very
likely, possible, doubtful and impossible.
(2) Analysis of adverse events and drug-relatedness
Sure
As likely as
not
Possible
Suspicious
Impossible
Have a
reasonable
chronological
order with the
medication
+
+
+
+
-
Known types of
drug response
+
+
+
+
-
The reaction
decreased or
disappeared after
drug withdrawal
+
+
±
±
-

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Reactions were
repeated after
re-administration
+
?
?
?
-
Cannot be
explained by
disease,
combination, etc
ten
+
+
-
±
-
Note: + means positive, - means negative, ±means positive or negative, ? means unclear
Special Note: The relationship between radiation dermatitis and adverse events in this
trial
(1) Dual Attribute Definition: The primary efficacy endpoint of this study was the incidence
of grade ≥2 radiation dermatitis. Therefore, radiation dermatitis was identified as both an
expected event and an efficacy observation indicator in this study.
(2) Safety record requirements: In accordance with the principle of comprehensive subject
safety assurance under GCP, all cases of radiation dermatitis occurring during the trial, regardless
of severity, must be objectively recorded as adverse events (AEs) for intergroup safety comparison
and analysis.
(3) SAE Reporting Principle: If radiation dermatitis meets the protocol-defined criteria for a
serious adverse event (SAE) (e.g., resulting in hospitalization or life-threatening conditions), the
SAE reporting procedure must be immediately initiated. This procedure is not exempted due to the
event being anticipated.

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IX. Other Notes
1. Establish a project management team with reasonable division of labor and clear tasks, and
appoint a project secretary to facilitate the arrangement of various clinical-related matters.
2. A dedicated archive cabinet should be established to properly store project documentation,
facilitating supervision and audits by regulatory authorities.
3. Ensure the authenticity and completeness of research data by promptly and meticulously
documenting study cases according to visit points, and timely entering them into the electronic
medical record (EMR) system. This facilitates early identification of potential issues in the study
and avoids last-minute documentation or entry of study cases.
4. Participation in medical research by individuals with capacity for informed consent must
be voluntary. Although consulting family members or community leaders may be appropriate, the
subject cannot be enrolled in the medical study unless they have given their free and informed
consent.
5. In medical research involving human subjects with capacity for informed consent, each
potential participant must be fully informed of the study objectives, methods, funding sources, any
potential conflicts of interest, the investigator's affiliation, expected benefits and potential risks of
the study, possible discomforts associated with the study, post-study safeguards, and any other
research-related matters. Potential participants must be informed of their right to refuse
participation in the study or to withdraw their consent at any time without retaliation. Special
attention should be paid to the specific information requirements of potential individual subjects
and the manner in which such information is communicated. All medical research subjects have
the right to be informed of the general outcomes and results of the study.
6. When obtaining informed consent for research participation, physicians should exercise
particular caution if the potential subject has a dependent relationship with the physician or may
consent under duress. If a potential subject deemed incapable of giving informed consent agrees to
participate in the study, the physician must additionally obtain consent from a legally authorized
representative. The objections raised by the potential subject should be respected.
7. Physicians must fully inform patients about which aspects of medical treatment are related
to the study. Patients' refusal to participate in the study or decision to withdraw should not
adversely affect the doctor-patient relationship.

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