[논문]Oral Glutamine Supplementation Reduces Radiotherapy-induced Esophagitis in Lung Cancer Patients

Gul, Kanyilmaz; Muge, Akmansu; Taner, Atasever; Sehri, Elbag

doi:10.7314/apjcp.2015.16.1.53

[해외논문] Oral Glutamine Supplementation Reduces Radiotherapy-induced Esophagitis in Lung Cancer Patients 원문보기

Asian Pacific journal of cancer prevention : APJCP, v.16 no.1, 2015년, pp.53 - 58

Gul, Kanyilmaz (Department of Radiation Oncology, Faculty of Medicine, Necmettin Erbakan University) , Muge, Akmansu (Department of Radiation Oncology, Faculty of Medicine, Gazi University) , Taner, Atasever (Department of Nuclear Medicine, Medipol Hospital) , Sehri, Elbag (Department of Pathology, Faculty of Medicine, Gazi University)

Abstract ▼ AI-Helper

Background: The purpose of this study was to assess the the efficacy of oral glutamine (GLN) in prevention of acute radiation-induced esophagitis in patients with lung cancer and determine the predictive role of clinical and dosimetric parameters. Materials and Methods: Thirty-two patients diagnosed with lung cancer were studied prospectively. Sixteen patients (50%) received prophylactic powdered GLN orally in doses of 10g/8h. Patients were treated 2 Gy per fraction daily, 5 days a week. We evaluated the grading of esophagitis daily at the end of each fraction of each treatment day until a cumulative dose of 50 Gy was reached. The primary end point was radiation-induced esophagitis. Results: All patients tolerated GLN well. Toxicity grade, weight loss, serum cytokine levels and esophageal transit times exhibited statistically significant improvement in the GLN receiving group. GLN suppressed the inflammation related to the disease and treatment and reduced toxicity with statistical significance. Conclusions: This study suggests a benefical role of oral GLN use in prevention and/or delay of radiation-induced esophagitis, in terms of esophageal transit time and serum immunological parameters, as well as weight loss.

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문제 정의

In another 46-patient retrospective study, Tutanc et al. aimed to understand the efficacy of oral GLN in the prevention of acute radiation-induced esophagitis in patients with lung cancer who are treated with thoracic radiotherapy. They reported the reduction of incidence and severity of acute radiation induced esophagitis during thoracic irradiation resulting from oral GLN with their datas (Tutanc et al.

가설 설정

Glutamine (GLN) is a neutral amino acid that acts as a substrate for nucleotide synthesis in most dividing cells such as enterocytes, lymphocytes, and fibroblasts as nitrogen source and/or alternative energy fuel. It is hypothesized that increased GLN demands of host, increase the capacity of endogenous production resulting in a strong GLN deprivation with detrimental effects on organ functions in cancer patients. In long term periods of cancer cachexia, an adequate nutrition support including GLN can essentially contribute to cover GLN needs and, thus to spare energy reserves of the host and to retard severe complications such as multi-organ failure.
Due to the significantly shorter ETT and reduction of esophageal side effects, we concluded in this study that GLN supplementation reduces local inflammation and motility disorders due to the reduction of inflammatory cytokines.

제안 방법

All patients had the following inclusion criteria: histopathologic proof of lung cancer, indication for definitive radiotherapy, age ≥18 and <80, Karnofsky Performance Status (KPS) ≥70, no prior history of thoracic RT, no pretreatment dysphagia or ingestion difficulties, not having received any other supplementary products, no known GLN allergy.
The purpose of this study was to assess the the efficacy of oral GLN in prevention of acute radiationinduced esophagitis in patients with lung cancer and to determine the predictive role of clinical (such as, serum immunological parameters and esophageal transit time) and dosimetric paramete.
GLN powder is one of the dietary supplements recommended to our patients. Sixteen patients in this study received prophylactic GLN powder (GLN Resource R, Nestle) at a dose of 30g/day (10g/8h orally, dissolved in water or fruit juices) starting one week before thoracic RT and continuing for two weeks after completion of RT. Although we planned to use glutamine in the entire study population,16 patients did not receive any supplementary products due to economical reasons or patients’ selfchoise.
In this study we assessed the efficacy of oral GLN in prevention of acute radiation-induced esophagitis in patients with lung cancer and determine the predictive role of clinical (eg., serum immunological parameters and esophageal transit time) and dosimetric parameters.
The treatment planning for eligible patients was based on gross tumor volume (GTV) which contained both the primary tumor and involved lymp nodes. Clinical target volumes (CTV) were defined by adding a 1cm margin to GTVs. Planning target volume (PTV)1 was defined by adding a 1cm margin to CTV and PTV2 was defined by adding a 1cm margin to GTV.
For the statistical analysis, the baseline demographic characteristics and patients were stratified according to whether GLN used. The following parameters were analyzed for correlation of acute esophagitis: age, gender, tumor stage, nodal stage, chemotherapy status, irradiated esophagus length, V5- V50 of esophagus. The rate of development of esophagitis with regard to primary parameter between treatment groups were evaluated using the chi-square test.
Esophageal scintigraphy was performed before and on the fifth week of RT to evaluate esophageal motility. Measurements were examined in three parts according to the anatomic structure of the esophagus.
Patients were compared according to changes in cytokine levels at the beginning and at the end of treatment. In order to evaluate the immunological parameters (TNF-alpha, IL-1beta, IL-6 and IL-8 levels were evaluated) of patients on the first and fifth weeks of treatment, blood samples were collected. Mean cytokine levels and the difference between pretreatment levels and end of treatment levels were evaluated (Table 2).
The purpose of this study was to assess the the efficacy of oral GLN in prevention of acute radiationinduced esophagitis in patients with lung cancer and to determine the predictive role of clinical (such as, serum immunological parameters and esophageal transit time) and dosimetric parameters.
A total dose of 5000 cGy in 25 fractions of 200 cGy was applied from four different portals to all patients. Esophageal motility was evaluated before and immediately after RT using esophageal scintigraphy. Post-irradiation therapy ETT values were significicantly higher compared to pre-radiation therapy ETT values (p<0.

데이터처리

Frequency distributions were compared by using either Chi-square test, Student’s t-test, Pearson’s exact test or Spearman’s correlations.
The following parameters were analyzed for correlation of acute esophagitis: age, gender, tumor stage, nodal stage, chemotherapy status, irradiated esophagus length, V5- V50 of esophagus. The rate of development of esophagitis with regard to primary parameter between treatment groups were evaluated using the chi-square test. In terms of other variables, the values obtained before treatment and during treatment, depending on the type of data were compared with the appropriate parametric or non-parametric tests.

성능/효과

There was no significant difference between GLNsupplemented and non-supplemented patients in terms of dosimetric parameters such as the mean esophageal dose, maximum esophageal point dose, irradiated esophagus length and volume, ratio of the irradiated length to total length of the esophagus in the field of treatment and ratio of the irradiated volume of esophagus to total volume of esophagus. In addition, the two groups were compared in terms of V5-V50.
A strong correlation between increasing age and esophagitis was found between each of the two subgroups, i.e. both the GLN-supplemented and nonsupplemented patients as well as in the grand total of all patients, but the results were not statistically significant. There was no significant correlation between esophagitis and T and N status and stage in the grand total of the patients.
There was a clear relationship between dose-volume parameters and esophagitis however there were no absolute parameters associated with esophagitis. In our study, V20,V25,V30,V35,V40 and V45 parameters were statistically significantly associated with esophagitis in GLN-non-supplemented group (respectively; p=0.042, p=0.042, p=0.042, p=0.033, p=0.033, p=0.033). Looking at the overall group, this relationship is lost.
(2009) investigated 41 lung cancer patients and 22 of them received prophylactic GLN. Patients were evaluated for weight changes at the beginning and at the end of treatment, GLN-non-supplemented patients had significant weight loss whereas, GLN-supplemented patients had statistically significant weight gain. In our study, 37.
In conclusion, the results of this study suggest a beneficial role of oral GLN use in prevention and/or delay of esophagitis incidence and severity due to suppression of the inflammatory process in lung cancer patients treated with definitive RT. In this way, toxicity was reduced and treatment-induced weight loss was decreased.
All values were seen to be higher in the group receiving GLN; V15, V20, V25 and V50 values demonstrated statistically significant elevation in GLN-supplemented group.

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