Zhixiong Lin

A longitudinal study on the radiation-induced thyroid gland changes after external beam radiotherapy of nasopharyngeal carcinoma.

BACKGROUND Radiation-induced thyroid disorders have been reported in radiotherapy of head and neck cancers. This study evaluated the radiation-induced damages to thyroid gland in patients with nasopharyngeal carcinoma (NPC). METHODS Forty-five patients with NPC treated by radiotherapy underwent baseline thyroid hormones (free triiodothyronine, free thyroxine [fT4], and thyrotropin [TSH]) examination and CT scan before radiotherapy. The volume of the thyroid gland was calculated by delineating the structure in the corresponding CT slices using the radiotherapy treatment planning system. The thyroid doses were estimated using the treatment planning system. Subsequent CT scans were conducted at 6, 12, and 18 months after radiotherapy, whereas the hormone levels were assessed at 3, 6, 12, and 18 months after radiotherapy. Trend lines of the volume and hormone level changes against time were plotted. The relationship between the dose and the change of thyroid volume and hormone levels were evaluated using the Pearson correlation test. RESULTS An average of 20% thyroid volume reduction in the first 6 months and a further 8% shrinkage at 12 months after radiotherapy were observed. The volume reduction was dependent on the mean thyroid doses at 6, 12, and 18 months after radiotherapy (r = -0.399, -0.472, and -0.417, respectively). Serum free triiodothyronine and fT4 levels showed mild changes of <2.5% at 6 months, started to drop by 8.8% and 11.3%, respectively, at 12 months, and became stable at 18 months. The mean serum TSH level increased mildly at 6 months after radiotherapy and more steeply after 18 months. At 18 months after radiotherapy, 12 patients had primary hypothyroidism with an elevated serum TSH, in which 4 of them also presented with low serum fT4. There was a significant difference (p = 0.014) in the mean thyroid doses between patients with hypothyroidism and normal thyroid function. CONCLUSIONS Radiotherapy for patients with NPC caused radiation-induced changes of the thyroid gland. The shrinkage of the gland was greatest in the first 6 months after radiotherapy, whereas the serum fT4 and TSH levels changed at 12 months. Radiation-induced changes were dependent on the mean dose to the gland. Therefore, measures to reduce the thyroid dose in radiotherapy should be considered.

Promoter hypermethylation of tumor suppressor genes in serum as potential biomarker for the diagnosis of nasopharyngeal carcinoma

PURPOSE Promoter hypermethylation of tumor suppressor genes may serve as a promising biomarker for the diagnosis of cancer. Cell-free circulating DNA (cf-DNA) shares hypermethylation status with primary tumors. This study investigated promoter hypermethylation of five tumor suppressor genes as markers in the detection of nasopharyngeal carcinoma (NPC) in serum samples. METHODS cf-DNA was extracted from serum collected from 40 NPC patients and 41 age- and sex-matched healthy subjects. The promoter hypermethylation status of the five genes (RASSF1, CDKN2A, DLEC1, DAPK1 and UCHL1) was assessed by methylation-specific PCR after sodium bisulfite conversion. Differences in the methylation status of these five genes between NPC patients and healthy subjects were compared. RESULTS The concentration of cf-DNA in the serum of NPC patients was significantly higher than that in normal controls. The five tumor suppressor genes - RASSF1, CDKN2A, DLEC1, DAPK1 and UCHL1 - were found to be methylated in 17.5%, 22.5%, 25.0%, 51.4% and 64.9% of patients, respectively. The combination of four-gene marker - CDKN2A, DLEC1, DAPK1 and UCHL1 - had the highest sensitivity and specificity in predicting NPC. CONCLUSION Screening DNA hypermethylation of tumor suppressor genes in serum was a promising approach for the diagnosis of NPC.

Longitudinal study on the correlations of thyroid antibody and thyroid hormone levels after radiotherapy in patients with nasopharyngeal carcinoma with radiation-induced hypothyroidism

The purpose of this study was to evaluate the correlations of thyroid antibody and thyroid hormone in postradiotherapy (post‐RT) patients with nasopharyngeal carcinoma (NPC).

Evaluation of clinical hypothyroidism risk due to irradiation of thyroid and pituitary glands in radiotherapy of nasopharyngeal cancer patients

Radiation‐induced thyroid dysfunction after radiotherapy for nasopharyngeal cancer (NPC) has been reported. This study investigated the radiation effects of the thyroid and pituitary glands on thyroid function after radiotherapy for NPC.

Nomogram for radiation-induced hypothyroidism prediction in nasopharyngeal carcinoma after treatment

OBJECTIVE The aim of this study was to develop a nomogram for radiation-induced hypothyroidism (RHT) prediction. METHODS We collected data from 164 patients with nasopharyngeal carcinoma (NPC) in our previous prospective study. Biochemical hypothyroidism was defined as a serum thyroid-stimulating hormone level greater than the normal value. We collected both clinical and dose-volume factors. A univariate Cox regression analysis was performed to identify RHT risk factors. Optimal predictors were selected according to the least absolute shrinkage and selection operator (LASSO). We then selected the Cox regression models that best balanced the prediction performance and practicability to build a nomogram for RHT prediction. RESULTS There were 38 (23.2%) patients who developed RHT, and the median follow-up was 24 months. The univariate Cox regression analysis indicated that gender, minimum dose, mean dose (Dmean) and V25-V60 [Vx (%), the percentage of thyroid volume receiving >x Gy] of the thyroid were significantly associated with RHT. The variables of gender, receiving chemotherapy or not (chemo), Dmean and V50 were selected using the LASSO analysis. A nomogram based on a three-variable (gender, chemo and V50) Cox regression model was constructed, and its concordance index was 0.72. Good accordance between prediction and observation was showed by calibration curves in the probability of RHT at 18, 24 and 30 months. CONCLUSION This study built a nomogram for RHT in NPC survivors by analyzing both clinical and dose-volume parameters using LASSO. Thus, the individual dose constraint could be achieved in a visual format. Advances in knowledge: This study used LASSO to more accurately address the multicollinear problem between variables. The resulting nomogram will help physicians predict RHT.

Optimizing the flattening filter free beam selection in RapidArc®-based stereotactic body radiotherapy for Stage I lung cancer.

OBJECTIVE To optimize the flattening filter-free (FFF) beam selection in stereotactic body radiotherapy (SBRT) treatment for Stage I lung cancer in different fraction schemes. METHODS Treatment plans from 12 patients suffering from Stage I lung cancer were designed using the 6XFFF and 10XFFF beams in different fraction schemes of 4 × 12, 3 × 18 and 1 × 34 Gy. Plans were evaluated mainly in terms of organs at risk (OARs) sparing, normal tissue complication probability (NTCP) estimation and treatment efficiency. RESULTS Compared with the 10XFFF beam, 6XFFF beam showed statistically significant lower dose to all the OARs investigated. The percentage of NTCP reduction for both lung and chest wall was about 10% in the fraction schemes of 4 × 12 and 3 × 18 Gy, whereas only 7.4% and 2.6% was obtained in the 1 × 34 Gy scheme. For oesophagus, heart and spinal cord, the reduction was greater with the 6XFFF beam, but their absolute estimates were <10(-6)%. The mean beam-on time for 6XFFF and 10XFFF beams at 4 × 12, 3 × 18 and 1 × 34 Gy schemes were 2.2 ± 0.2 vs 1.5 ± 0.1, 3.3 ± 0.9 vs 2.0 ± 0.5 and 6.3 ± 0.9 vs 3.5 ± 0.4 min, respectively. CONCLUSION The 6XFFF beam obtains better OARs sparing and lower incidence of NTCP in SBRT treatment of Stage I lung cancer, whereas the 10XFFF beam improves the treatment efficiency. To balance the OARs sparing and intrafractional variation owing to the prolonged treatment time, the authors recommend using the 6XFFF beam in the 4 × 12 and 3 × 18 Gy schemes but the 10XFFF beam in the 1 × 34 Gy scheme. ADVANCES IN KNOWLEDGE This study optimizes the FFF beam selection in different fraction schemes in SBRT treatment of Stage I lung cancer.

Effect of beam arrangement on oral cavity dose in external beam radiotherapy of nasopharyngeal carcinoma

This study compared the oral cavity dose between the routine 7-beam intensity-modulated radiotherapy (IMRT) beam arrangement and 2 other 7-beam IMRT with the conventional radiotherapy beam arrangements in the treatment of nasopharyngeal carcinoma (NPC). Ten NPC patients treated by the 7-beam routine IMRT technique (IMRT-7R) between April 2009 and June 2009 were recruited. Using the same computed tomography data, target information, and dose constraints for all the contoured structures, 2 IMRT plans with alternative beam arrangements (IMRT-7M and IMRT-7P) by avoiding the anterior facial beam and 1 conventional radiotherapy plan (CONRT) were computed using the Pinnacle treatment planning system. Dose-volume histograms were generated for the planning target volumes (PTVs) and oral cavity from which the dose parameters and the conformity index of the PTV were recorded for dosimetric comparisons among the plans with different beam arrangements. The dose distributions to the PTVs were similar among the 3 IMRT beam arrangements, whereas the differences were significant between IMRT-7R and CONRT plans. For the oral cavity dose, the 3 IMRT beam arrangements did not show significant difference. Compared with IMRT-7R, CONRT plan showed a significantly lower mean dose, V30 and V-40, whereas the V-60 was significantly higher. The 2 suggested alternative beam arrangements did not significantly reduce the oral cavity dose. The impact of varying the beam angles in IMRT of NPC did not give noticeable effect on the target and oral cavity. Compared with IMRT, the 2-D conventional radiotherapy irradiated a greater high-dose volume in the oral cavity.

Effects of omitting elective neck irradiation to nodal Level IB in nasopharyngeal carcinoma patients with negative Level IB lymph nodes treated by intensity-modulated radiotherapy: a Phase 2 study

OBJECTIVE To investigate the need for elective neck irradiation (ENI) to nodal Level IB in patients with nasopharyngeal carcinoma (NPC) with negative Level IB lymph nodes (IB-negative) treated by intensity-modulated radiotherapy (IMRT). METHODS We conducted a Phase 2 prospective study in 123 newly diagnosed IB-negative patients with NPC treated by IMRT, who met at least 1 of the following criteria: (1) unilateral or bilateral Level II involvement with 1 of the following: Level IIA involvement or any Level II node ≥2 cm/with extracapsular spread; (2) ≥2 unilateral node-positive regions. Bilateral Level IB nodes were not contoured as part of the treatment target and treated electively. Level IB regional recurrence rate; pattern of treatment failure; 3-year overall survival (3y-OS), 3-year local control (3y-LC) and 3-year regional control (3y-RC) rates; toxicities; and dosimetric data for planning target volumes, organs at risk, Level IB and submandibular glands (SMGs) were evaluated. RESULTS Two patients developed failures at Level IB (1.6%). The 3y-LC, 3y-RC and 3y-OS rates were 93.5%, 93.5% and 78.0%, respectively. Bilateral Level IB received unplanned high-dose irradiation with a mean dose (Dmean) ≥50 Gy in 60% of patients. The average Dmean of bilateral SMGs was approximately 53 Gy. CONCLUSION ENI to Level IB may be unnecessary in IB-negative patients with NPC treated by IMRT. A further Phase 3 study is warranted. ADVANCES IN KNOWLEDGE Based on the results of this first Phase 2 study, we suggest omitting ENI to Level IB in Ib-negative patients with NPC with extensive nodal disease treated by IMRT.

Evaluation of the dosimetric impact of applying flattening filter‐free beams in intensity‐modulated radiotherapy for early‐stage upper thoracic carcinoma of oesophagus

Flattening filter‐free (FFF) radiation beams have recently become clinically available on modern linear accelerators in radiation therapy. This study aimed to evaluate the dosimetric impact of using FFF beams in intensity‐modulated radiotherapy (IMRT) for early‐stage upper thoracic oesophageal cancer.

Clinical characteristics and prognostic factors of esophageal carcinoma associated with multiple primary carcinomas: a report of 268 cases

Background: To evaluate the clinical characteristics and prognostic factors of esophageal carcinoma (EC) with multiple primary carcinomas (ECWMPC). Methods: Clinical and survival data of 268 ECWMPC patients with two different primary carcinomas and 9,101 individual EC patients taken from hospital records dating from January 1996 to December 2012 were analyzed retrospectively. Results: There were a total of 11,066 EC patients treated over this period of which 330 patients met the diagnostic criteria of ECWMPC. Two hundred and sixty-eight patients who had two different primary carcinomas and survival data were recruited in this analysis. The median age of the first carcinoma occurrence was 59 (31 to 85) years old, and the median age of the second carcinoma occurrence was 62 (32 to 86) years old, with a male to female ratio of 6:1. The predilection sites were located in the head and neck, followed by the gastric-esophageal junction. For the subgroup of synchronous ECWMPC (S-ECWMPC) and metachronous ECWMPC (M-ECWMPC), head and neck remain the popular site of S-ECWMPC but cardiac became the top of the M-ECWMPC. More breast and colon rectum disease were found in S-ECWMPC patients. The ECWMPC patients had a significantly lower median survival time (MST) and 1, 3, and 5 years overall survival (OS) than the single EC patients [12.4 months and 51.8%, 21.9%, 14.7% vs . 17.0 months and 59.4%, 31.3%, and 23.9% (P vs . 13.9 months and 56.2%, 25.6%, 19.5% (P=0.001)]. Within the S-ECWMPC group, patients who only received radiotherapy and/or chemotherapy (RoC) (n=52) had a shorter/poorer survival time (MST and 1, 3, and 5 years OS are 9.8 months, 44.2%, 8.7%, 3.2%) compared to patients who received surgery (n=43) (MST and 1, 3, and 5 years OS are 16.4 months, 64.8%, 33.3%, 18.6%) (P=0.031), but a longer survival time compared to patients who had no treatment (n=20) (MST and 1, 3, and 5 years OS are 4.1 months, 10.0%, 5.0%, and 0%)(P=0.002). Within the M-ECWMPC group, patients who had received surgery (n=103) had a longer survival time than patients who had only received RoC (n=38) (MST 22.5 vs . 10.6 months, P=0.026). Among the 103 M-ECWMPC patients who had received surgery, 55 of them had an esophagus resection, whose OS was similar to those 3,633 operated EC patients (MST 31 months vs . 30 months, P=0.905). Within the M-ECWMPC group, patients with greater than 3 years interval time of diagnosis (ITD) had a better prognosis compared to patients with less than 3 years ITD (MST 24.8 vs . 13.2 months, P=0.021) There is no statistical difference in the prognosis between M-ECWMPC patients and Single EC patients (P=0.585). Conclusions: ECWMPC is not rare among EC patients. There is more cardiac in the M-ECWMPC patients and more Breast and Colon rectum disease were found in S-ECWMPC patients. Prognosis of M-ECWMPC patients was better than that of the S-ECWMPC patients. M-ECWMPC patients with a more than 3 years ITD had a better prognosis. In M-ECWMPC patients, esophageal surgery can acquire better survival benefits than other treatments. Surgery is highly recommended for ECWMPC patients.