2.1 Patient and the study setting:
From May 2012 to December 2018, a total of 93 patients with hypopharyngeal cancer who were undergoing radiotherapy were identified. They were staged IIB-IVA (8th edition AJCC Hypopharyngeal cancer TNM staging standard was referenced for staging). Patients inclusion criteria: previously untreated with hypopharyngeal cancer, staging IIB-IVA; completed radiotherapy and the records of acute toxicities were available; pathologically diagnosed hypopharyngeal cancer squamous cell carcinoma; there were no distant organ metastasis proved by MRI/CT examination; KPS (pretreatment Karnofsky score) ≥70; blood tests, kidney and liver function were in normal range. Patients exclusion criteria: patients have history of drug allergy; patients with others tumor. Clinical characteristics and relative data of patients were collected from the records. All subjects in present study had signed informed consent before they accepted treatment. This study was approved by the Ethical Committee of Affiliated Cancer Hospital of Zhengzhou University.
2.2 Variables
Patient’s gender, age, BMI, history of cigarettes smoking and alcohol consumption, hypotension, diabetes mellitus, treatment regimens (RT alone, IC, CCRT, IC+ CCRT), post-operative radiotherapy, T staging, N staging, subsite (posterior pharyngeal, post cricoid region, pyriform sinus), GTV total dosage (Gy), GTV fraction dosage (Gy), as well as hemoglobin value (1 week before radiotherapy) were extracted from clinical records for investigation.
2.3 Treatment:
Radiotherapy Treatment: Patients were all accepted for conformal intensity modulated radiation therapy using 6MV x-ray medical linear accelerator (Varian company) as standard treatment modality. The prescription dose for gross tumor volume, including prime site of tumor and involved lymph nodes (GTVnx / GTVnd), ranges from 60 to 70Gy, with daily fraction dose of 2.0 - 2.2 5Gy, and 5 fractions per week. Prescription dose of clinical target volume (CTV) ranges from 50.4Gy to 60Gy. Normal tissues were managed with tolerable RTOG0615 and RTOG0225 normal tissue limit dosage[5].
Chemotherapy Treatment: Chemotherapy protocols include induction chemotherapy alone (IC), concurrent chemotherapy (CRT), and induction chemotherapy + concurrent chemotherapy (IC + CRT). 2 ~ 3 cycles chemotherapy were prescribed with each modality. Chemotherapy regimens include “TP”, “DF”, “P”. (TP: Cisplatin: 70~80mg-/m2, d1, Docetaxel: 100~120mg, d1; DF: cisplatin: 70~80mg/m2, d1, 5-Fu: 750mg/m2, d1-5; P: Cisplatin 70~80mg/m2, d1).
2.4 Management of radiation induced oral toxicities
Oral care was delivered to subjects with OM (once a day); compound VitminB12 solution was compressed and used for atomization inhalation; recombinant fibroblast growth factor 1(Acidic, FGF1) local spraying and antibiotic were used for patients of G3 OM. Antibiotics usage was based on throat swab culture results. Oxycodone hydrochloride prolonged-release tablets was administered when pain score of patients was up to 4. In severe situations, fentanyl would be applied for patients, and patients would be suggested to discontinue RT for 2 to 3 days (no more than 5 days) if even worse.
2.5 Radiation reaction and criteria
RTOG standard for acute radiation mucositis and dermatitis were used for grading [6, 7] (Table 1); G0 ~ G1was defined as mild adverse reaction; G2 ~ G4 was defined as acute adverse reaction ( there is no one with grade 4 in this study).
2.6 Statistical analysis
Statistical analysis were carried out using SPSS 25 (IBM, Armonk, NY). Each variable was analyzed by univariate Cox regression, Student T-Test and Chi square test (or Fisher’s exact test) for continuous quantitative data and categorical variables respectively. The variables were considered correlated with oral mucositis when p < 0.05, and these variables were put into the multivariable Cox regression model to identify independent risk factors. Two-tailed test p < 0.05 were considered statistically significant.
Table 1 RTOG Standards for radiation mucositis and radiation dermatitis
Grade
|
Oral mucosa reaction
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Acute radiation dermatitis
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Grade 0
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no change
|
No change over baseline
|
Grade 1
|
Irradiation/ may experience mild pain not
|
Follicular, faint or dull erythema /epilation
|
|
requiring analgesic
|
/dry desquamation/decreased sweating
|
|
|
|
Grade 2
|
Patchy mucositis that may produce an
|
Tender or bright erythema, patchy moist
|
|
inflammatory serosanguinous discharge may
|
desquama moderate edema
|
|
experience moderate pain re-quiring narcotic
|
|
Grade 3
|
Confluent fibrinous mucositis may induce
|
Confluent, moist desquamation other than
|
|
severe pain requiring narcotic
|
skin folds, pitting edema
|
Grade 4
|
Ulcer, hemorrhage or necrosis
|
Ulceration, hemorrhage, necrosis
|