Abstract—The purpose of this study is to derive parameters estimating for the Lyman–Kutcher–Burman (LKB) normal tissue complication probability (NTCP) model using analysis of scintigraphy assessments and quality of life (QoL) measurement questionnaires for the parotid gland (xerostomia). In total, 31 patients with head-and-neck (HN) cancer were enrolled. Salivary excretion factor (SEF) and EORTC QLQ-H&N35 questionnaires datasets are used for the NTCP modeling to describe the incidence of grade 4 xerostomia. Assuming that n= 1, NTCP fitted parameters are given as TD50= 43.6
Gy, m= 0.18 in SEF analysis, and as TD50= 44.1 Gy, m= 0.11 in QoL
measurements, respectively. SEF and QoL datasets can validate the Quantitative Analyses of Normal Tissue Effects in the Clinic (QUANTEC) guidelines well, resulting in NPV’s of 100% for the both datasets and suggests that the QUANTEC 25/20Gy gland-spared guidelines are suitable for clinical used for the HN cohort to effectively avoid xerostomia.
Keywords—HN, NTCP, SEF, QoL, QUANTEC
I. INTRODUCTION
EAD and neck (HN) cancer is a one of the leading causes of cancer mortality in Taiwan. Radiotherapy (RT) plays an important role in the treatment of HN cancer. Xerostomia is a common complication that occurs after RT for patients with HN cancer. Severe xerostomia is defined as long-term salivary function compared to the pre-RT baseline which based-on the Late Effects of Normal Tissues–Subjective, Objective, Management, Analytic (LENT-SOMA) criteria.
Whole-mouth salivary function has been shown to relate to quality of life (QoL) measurement questionnaires [1-2], and has been used in clinical oncology trials to compare different treatment strategies. In this prospective study, we longitudinally observed the parotid glands function by using salivary scintigraphy in patients receiving intensity modulated radiotherapy (IMRT).
TFL, HMT, PJC, JCJ, MYC, and LCC are with the National Kaohsiung University of Applied Sciences. (*Corresponding author: TFL, phone: 886-7-3814526; fax: 886-7-3811186; E-mail: [email protected];
§ contributed equally)
HMT and PJC are with the Department of Radiation Oncology, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine (e-mail: [email protected]).
WCC and LCC are the Department of Radiation Oncology, Chang Gung Memorial Hospital-Chiayi Medical Center, Chang Gung University College of Medicine.
JMW is with the Department of Information Engineering, I-Shou University, Taiwan and the Department of Radiation Oncology, E-Da Hospital, Kaohsiung, Taiwan. § contributed equally
The normal tissue complication probability (NTCP) model proposed by Lyman will be used to determine the TD50 of parotid gland in local patients [3-4]. Moreover, patients-reported QoL questionnaire (QLQ-C30) and xerostomia-specific questionnaire (QLQ-H&N35) were given to patients before RT and periodically after therapy to assess their interrelationships with salivary function. NTCP fitted parameters are investigated for the local patients by the two datasets.
The Quantitative Analyses of Normal Tissue Effects in the Clinic (QUANTEC), a recent concerted effort in radiotherapy community, which reviewed and summarized normal tissue toxicity, and might suggest dose–volume treatment planning guidelines likely to be reduced the rates of side effects. QUANTEC guideline to limit the probability of severe xerostomia fit these criteria are: at least one parotid gland should receive ≤20Gy mean dose, or both parotid glands should receive ≤25Gy mean dose [5-6]. Therefore, we also perform a validation test of these QUANTEC guidelines against prospectively collected QoL datasets and salivary scintigraphic assessments in this study.
II. METHODS AND MATERIALS
A. Study Population
A total numbers of 31 HN cancer patients who treated with IMRT at the Chiayi Chang Gung Memorial Hospital of the Chang Gung Medical Foundation, between May 2007 and Oct 2010 were used. The characteristics of patients are listed in Table I. Patients with successful salivary flow scintigraphy imaging and completion of QoL questionnaires before and at 1-year after treatment were analyzed. This study was approved by the institutional review board of the hospital (IRB-95-1430B).
B. Treatment Techniques
Patients were immobilized from head to shoulders using commercially available thermoplastic masks and/or an individually customized bite block. Computed tomography (CT) images (2.5-mm slice thickness) acquired from the top of the vertex to the level of the carina, containing 512×512 pixels in each slice, were used. Both parotid glands were delineated by a radiation oncologist. The dose distributions were calculated and separate dose–volume histograms (DVHs) were generated for both parotid glands, and enabled the analysis of each gland separately. IMRT treatment mode was used in a simultaneous integrated boost (SIB) treatment method [7].
Model Parameters Estimating on
Lyman–Kutcher–Burman Normal Tissue
Complication Probability for Xerostomia on
Head and Neck Cancer
Tsair-Fwu Lee , Hui-Min Ting , Pei-Ju Chao, Jing-Chuan Jiang, Min-Yuan Chao, Wen-Cheng Chen,
Long-Chang Chen, Jia-Ming Wu
H
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IV. DISCUSSION
Figures and Tables For the LKB NTCP modeling, the local TD50 fitted parameters for 1-year after RT are given equal to 43.6 Gy for SEF analysis and 44.1 Gy for QoL assessments, respectively; they are higher than the report of Moiseenko et al. proposed, which is equal to 32.4 Gy. Whole-mouth salivary function has been shown to relate to QoL measurement questionnaires [1]. Deasy et. al. reported that a wide variation in the reported TD50 values (from 28.4 to 52 Gy) is unexplained but could result from several reasons, including differences in dose distributions, salivary measurement methods, segmentation, intragland sensitivity, and may differ from the living areas [5-6].
Xerostomia-specific questionnaires were found reliable and valid in measuring patient reported xerostomia [2]. In this study, Qol analyses were found valid in NTCP parameters modeling as SEF assessments. Pearson's chi-square test was used to test the association between two analysis methods. The p-value higher than the 0.05 criterion is said which corresponds to the variables having an association or relationship, imply SEF assessments and QoL analysis with similar result.
For IMRT planning goal, the mean dose to each parotid gland should be kept as low as possible, consistent with the desired clinical target volume coverage. Our study found that the incidence of grade 4 xerostomia is only ≈1% and ≈2% at 1-year for the QUANTEC recommendation of 20 Gy and 25 Gy respectively. Severe xerostomia can normally be avoided if at least one parotid gland has been spared to a mean dose ≤20 Gy or if both glands have been spared to a mean dose ≤25 Gy [6]. A lower parotid mean dose usually results in better function with respect to the effects on patient’s QoL.
V. CONCLUSION
Our study provides agreements with such SEF analysis and QoL assessments for the NTCP parameters modeling and QUANTEC guidelines validation. Based on these results, we believe that the clinical use of the QUANTEC 25/20Gy spared-gland–mean-dose guideline is useful for the HN cohort.
ACKNOWLEDGMENT
This study was supported financially, in part, by grants from the National Science Council (NSC101-2221-E-151-007-MY3 ) of the Executive Yuan of the Republic of China.
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