Chinese-German Journal of Clinical Oncology February 2012, Vol. 11, No. 2, P72–P75DOI 10.1007/s10330-011-0896-2

The morbidity and mortality of lung cancer are at fore-front in domestic and foreign. About 75% to 85% of the patients have lost the chance of operation time when di-agnosed. Radiotherapy is one of the main treatments to these patients, but local control rate and survival rate are low. Increasing dose is expected to improve local control rate and improve survival rate. Three-dimensional con-formal radiation therapy (three-dimensional conformal radiation therapy, 3D-CRT) can improve target dose. It may be appropriate to reduce the surrounding normal tis-sue dose, thereby reducing the incidence of chronic tox-icity [1]. But radiation pneumonitis (radiation pneumoni-tis, RP) as one of the main side effects of radiotherapy, has got clinical widespread concern. This study selected III non-small cell lung cancer (NSCLC) receiving different radiotherapy reduced field additional doses plan. In order to investigate RP differences occurred after CT/CT image fusion, to provide a reference basis for NSCLC additional doses of local radiation.

Materials and methods

PatientsWe studies a total 40 cases of NSCLC patients from

June 2006 to September 2008. The inclusion criteria into the group was: histological or cytological proved NSCLC; According to the 1997 AJCC stage was IIIA, IIIB period. There was no chance to have surgery but to accept the 3D-CRT; clinical and pathological information was com-plete; KPS score was over 60; no serious cardiopulmonary dysfunction; without chronic lung disease; in the course of radiotherapy, no distant metastasis; the patient has less than one week interruption during radiotherapy treat-ment; mass after radiotherapy doses 4000 cGy reduced 25%. Randomly divided into two groups: A group of 20 patients: age 45 to 70 years (median age, 58.3 years), 11 cases of squamous cell carcinoma, 7 cases of adenocarci-noma, other 2 cases, IIIA in 12 patients, IIIB in 8 cases; B group 20 patients: age ranged from 43 to 71 years (median age, 59.5 years), 12 cases of squamous cell carcinoma, ad-enocarcinoma in 7 cases, the other one case, IIIA of the 9 patients, IIIB of 11 cases.

Study of the impact of CT/CT image fusion radiotherapy on V20 and radiation pneumonitis of non-small cell lung cancerLiang Liu, Jinzhong Zhang, Changhu Li, Wei Ge, Shunxiang Luo, Yu Huang, Yongfa Zheng

Center of Oncology, Renmin Hospital of Wuhan University, Wuhan 430060, China

Received: 27 August 2011 / Revised: 20 September 2011 / Accepted: 24 October 2011© Huazhong University of Science and Technology and Springer-Verlag Berlin Heidelberg 2012

Abstract Objective: The aim of our study was to investigate the value of CT/CT image fusion radiation treatment planning in non-small cell lung cancer (NSCLC) and the impact on V20 and radiation pneumonitis (RP). Methods: Patients who were pathologically or cytologically diagnosed of stage IIIA and IIIB NSCLC were treated with three-dimensional conformal radiation therapy (4000 cGy). Forty patients got at least 25% tumor reduction were randomly divided into two groups: group A of regular shrink field radiotherapy (20 cases) and group B of CT/CT image fused shrink field radiotherapy (20 cases). Dosage reached 6600 cGy. Clinical data, V20 and RP were observed within 3 months after radiotherapy. Statistical analysis was conducted for the NSCLC patients. Results: 22.5% (9/40) patients got RP during follow-up. Group A accounted for 6 cases (30%), and group B had 3 cases (15%). There was no marked difference between the two groups (P = 0.256), univariate analysis revealed that the IV20 of A and B groups, and IV20 and CV20 of all patients were statistically related to the incidence of RP (P < 0.05). With Wilcoxon method assay, the ipsilateral lung V20 and contralateral lung V20 had statistical significance between the two groups (P < 0.05). Conclusion: The CT/CT image infusion treatment planning could increase the radical dosage with better tumor control probability but won’t increase adverse reaction.

Key words non-small cell lung cancer; three-dimensional conformal radiation therapy; radiation pneumonitis; CT/CT image fusion; V20

Correspondence to: Ge Wei. Email: gewei514@126.com

73Chinese-German J Clin Oncol, February 2012, Vol. 11, No. 2

Instrument and equipment Company Xio 4.2.2 U.S. CMS or the U.S. company

Eclipse 8.6 Varian treatment planning system; FocalPro 4.2.0 doctor workstation of treatment planning system; thermoplastic film with a hole in its body and body fixed plate Hip Fix produced by American Med-Tee company; using magic cross positioning method, when CT scan-ning, CT-Spot; marker was affixed to the center of the magic cross, GE Highspeed spiral CT; scanning and image parameters were 120 kV, 100 mA, matrix 512 × 512; scan spacing was 5 mm.

The design of radiation treatment planning The patients in the group were treated with full con-

ventional fractionated 3D-CRT (200 cGy/time, 1 times/day, 5 times/week), before treatment and reduced field in the course of the treatment, gave the CT localization scan respectively (covering the whole lung volume and the up-per and lower bounds, respectively, based on the outside into 5 cm). CT images in the treatment planning system might have a three-dimensional reconstruction before ra-diotherapy (Fig. 1a), target delineation, program design and evaluation, acquire he first programs of the first pro-cess of radiotherapy, gave prescription dose of 4000 cGy, target dose 95% isodose line. At the end of the first ra-diation therapy process, whose tumor size reducing 25%. Patients having the first 2 CT scan obtained CT images before radiotherapy reduced fields. A group separately use the 2nd CT images (Fig. 1b). Re-establish the data of patient, made a program design and evaluation indepen-dently, got the second scheme reduced fields of radiother-apy, an additional dose to 6600 cGy. B group would enter the 2nd CT images in treatment planning system. So CT images before radiotherapy would be a benchmark, the CT images as a reference field before shrinking, through the planning system coming with pixel registration algo-rithm and manual adjusting method to combine image fusion. CT/CT fusion image (Fig. 1c). Target delineation using image fusion got integration plans of shrinking field radiotherapy, an additional dose to 6600 cGy.

The treatment plan evaluation and observation As the evaluation indicators of V20 and the incidence of

RP were selected as observed indicators within 3 months after the end of radiotherapy, RP evaluation points were

judged by the standards of RTOG acute radiation injury.

Statistical analysis of data Using SPSS 11.5 statistical software for statistical anal-

ysis. Clinical indicators were tested by χ2. Using Mann-Whitney to test the correlation between V20 and RP, comparison between the two groups using Wilcoxon test V20. That the difference of was statistically significant.

Results

RP incidence and the single-factor analysis of clinicopathologic features

The RP rate of 40 patients enrolled was 22.5% (9/40), A group in which there were 6 patients (30%), B group 3 patients (15%). No significant difference between the two groups (P = 0.256). The data presented in Table 1.

The effect of V20 on the incidence of RPV20 of ipsilateral lung of cases in the A, B group were

associated with the incidence of RP, the difference was statistically significant (P = 0.001, 0.012); all patients, the contralateral lung V20, ipsilateral lung V20 were always re-lated to the incidence of RP. The difference was statisti-cally significant (P = 0.041, 0.000). The data presented in Table 2.

Comparison between the V20 of two groupsUsing Wilcoxon test, differences between ipsilateral

lung V20 (37.01 ± 7.86 vs. 35.09 ± 7.19) and contralateral lung V20 (15.55 ± 5.19 vs. 13.95 ± 6.08) of A B two groups were statistically significant (P = 0.028, 0.047), ipsilateral lung V20 and contralateral lung V20 of B group fusion group are lower.

Discussion

Radiation therapy is one of the primary treatments of NSCLC. Radiation therapy plays an important role in the treatment of locally advanced or inoperable NSCLC [2, 3]. More than 60% of the NSCLC patients in different stages of treatment need to receive radiotherapy. Studies show that raising the radiation dose can bring better local con-trol, 3D-CRT can let the tumor tissue obtain the average high dose irradiation, normal tissue are less susceptible

Fig. 1 Comparison of target contour based on different CT images. (a) The first CT image; (b) The second CT image; (c) The fusion CT image

74 www.springerlink.com/content/1613-9089

to or expect from unnecessary exposure [4]. However, oc-currence of RP is a limiting factor of increasing radiation dose of NSCLC. Severe irreversible RP of the patients will result in death [5].

Dose volume histogram (DVH graph) can provide a quantitative dose-volume and dose distribution rela-tionship for normal lung tissue under which the differ-

ent treatment plans can be generated to determine the possible differences in RP. In a prospective study, RTOG found that lung V20 was not only related to the incidence of RP, but also significantly related to severity of RP [6–8], that is, V20 < 22%, 22%–31%, 32%–40% and > 40% of the RP rates were 0.7%, 13% and 36%. All fatal RP occurred in the patients of V20 > 35%, and severe RP occurred in patients of V20 32%, after multivariate analysis, V20 is the only independent radiation-induced lung injury factor [9,

10]. Tsujino forward-looking analyses RP incidence of 71 patients of lung cancer who received radical radiother-apy. Univariate and multivariate analysis revealed that V20 was correlated with the occurrence of RP, including multivariate analysis, V20 is the single independent factor of RP incidence. Zhu and other researchers have reached similar results, so we have the V20 as a program evaluation indicator. In this study, univariate analysis found that ip-silateral lung V20 and contralateral lung V20 are correlated with the occurrence of RP, which stays consistent with Yang’ studies and other researcher’ studies [11, 12].

Studies have shown that local control rate of radio-therapy for NSCLC is only 15% to 17%. Local control failure is a major cause of death. The higher the radiation dose, the higher the local control rate of tumor. RP limit the occurrence of radiation dose of chest tumor, affecting the local control rate of the tumor, which urgently need a new radiotherapy technique or program design, without increasing the RP occurrence. Increase radiation dose to get out a good local control rate. Li and Ge, have con-firmed that CT/CT image fusion can be more direct and accurate to assess the amount of organs at risk throughout the course [13, 14]. So it can better guide clinical treatment from the perspective of radiological physics. We are try-ing to investigate its impact on RP and V20 from radiobio-logical point of view.

The study between the two groups have no significant difference in the incidence of RP, may be associated with quite homogeneous prescription dose (6600 cGy) and small sample size. The study also shows that fusion did not increase the incidence of RP. Wilcoxon test the dif-ference of V20 between the ipsilateral and contralateral groups were significant in statistics [15]. The fusion group is lower. Low V20 provide the conditions to further in-crease the local dosage and local control rate. So the CT/CT image fusion has a certain application in radiother-apy for NSCLC. Semenenko found that large volume of low-dose radiation exposure t are severer than the high dose of the small size of rat lung injury through animal researches.

CT/CT image fusion can make most of the rays shoot along the original “ballistic” while the local dosage in-creasing. On the volume of normal lung tissue injury is relatively small, benefit more. For the radiotherapy pa-tients implementing integration plans, the long-term out-

Table 1 Univariate analysis of the occurrence of RP and clinical and pathological features [case (%)]Clinicopathological parameters n RP χ2 P

Gender 0.001 0.982Male 31 7 (22.6)Female 9 2 (22.2)

Age (years) 0.014 0.905< 60 26 6 (23.1)≥ 60 14 3 (21.4)

Weight loss 0.399 0.527Yes 17 3 (17.6)No 23 6 (26.1)

Smoking history 0.335 0.563Yes 12 2 (16.7)No 28 7 (25.0)

Combined with chemotherapy 0.833 0.364Yes 26 7 (26.9)No 14 2 (14.3)

KPS score 0.086 0.769< 80 15 3 (20.0)≥ 80 25 6 (24.0)

Location of the tumor 0.162 0.687 Superior lobe 29 7 (24.1) In the lower lobe (Mediastinal type) 11 2 (18.2)Clinical stage 0.043 0.853

IIIA 21 5 (23.8)IIIB 19 4 (21.1)

Group 1.29 0.256 A 20 6 (30.0) B 20 3 (15.0)RP, radiation pneumonitis

Table 2 Correlation of V20 and the occurrence of RP (χ ± s)

GroupRP

PPositive NegativeA group Uninjured side V20 17.50 ± 5.17 14.71 ± 5.21 0.287 Injured side 48.17 ± 11.92 32.21 ± 6.12 0.001B group Uninjured side V20 19.67 ± 5.69 12.94 ± 6.15 0.095 Injured side V20 45.67 ± 10.21 33.23 ± 6.56 0.012Full set Uninjured side V20 18.22 ± 5.09 13.74 ± 5.72 0.041 Injured side V20 47.33 ± 10.79 33.77 ± 6.33 0.000RP, radiation pneumonitis

75Chinese-German J Clin Oncol, February 2012, Vol. 11, No. 2

come of patients with radiation and toxicity studies will have a more in-depth study in the following research.

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