Ju-Young Song

Metabolic Response of Lymph Nodes Immediately After RT Is Related With Survival Outcome of Patients With Pelvic Node-Positive Cervical Cancer Using Consecutive [18F]fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography

PURPOSE To evaluate the metabolic response of uterine cervix and pelvic lymph nodes (LNs) using consecutive 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (PET/CT) immediately after RT and to correlate survival outcome with the metabolic response. METHODS AND MATERIALS We retrospectively reviewed 48 patients with cervical cancer who had positive pelvic LNs by preradiation therapy (pre-RT) PET/CT. All patients underwent PET/CT scans immediately after RT (inter-RT PET/CT) after median 63 Gy to the gross LNs. The metabolic response of the LNs was assessed quantitatively and semiquantitatively by measurement of the maximal standardized uptake value (SUVmax). RESULTS Classifying the metabolic response of all nodal lesions, 37 patients (77%) had LNs with complete metabolic response on the inter-RT PET/CT (LNCMRi), and 11 patients had a non-LNCMRi, including 4 patients with progressive metabolic disease. The overall 3-year survival rates were 83% for the patients with LNCMRi and 73% for the non-LNCMRi group (P=.038). The disease-free survival for patients with LNCMRi were significantly better than that for the non-LNCMRi group (71% vs 18%, respectively, P<.001). The 3-year distant metastasis-free survival rates were 79% for the patients with LNCMRi and 27% for the non-LNCMRi group (P<.001). There were no statistically significant differences in overall survival (76% vs 86%, respectively, P=.954) and disease-free survival rates (58% vs 61%, respectively, P=.818) between the CMR of primary cervical tumor and the non-CMR groups. CONCLUSIONS The results showed a significant correlation between survival outcome and the interim metabolic response of pelvic LNs. CMR of nodal lesion on inter-RT PET/CT had excellent overall survival, disease-free survival and distant metastasis-free survival rates. This suggested that PET/CT immediately after RT can be a useful tool for the evaluation of the interim response of the LNs and identify a subset of patients with a high risk of recurrence and poor survival in patients with cervical cancer with initial positive LNs.

The metabolic response using 18F-fluorodeoxyglucose-positron emission tomography/computed tomography and the change in the carcinoembryonic antigen level for predicting response to pre-operative chemoradiotherapy in patients with rectal cancer.

BACKGROUND AND PURPOSE To predict tumor regression in pre-operative chemoradiotherapy (CRT) using (18)F-fluorodeoxyglucose-positron emission tomography/computed tomography (PET/CT) and serum carcinoembryonic antigen (CEA) in patients with rectal cancer. MATERIALS AND METHODS The metabolic response of the tumor was assessed by determining the maximal standardized uptake value (SUV(max)), absolute difference (ΔSUV(max)), and SUV reduction ratio (SRR) on pre- and post-CRT PET/CT scans. The serum CEA, absolute difference (ΔCEA), and the CEA reduction ratio (CRR) were also determined. A receiver-operating characteristic (ROC) curve was generated. RESULTS Of all seventy two patients, mean pre- and post-CRT SUV(max) was 14.9 and 5.8, respectively. The mean pre- and post-CRT CEA level was 15.5 ng/ml and 5.4 ng/ml, respectively. Forty-three patients (59.8%) were classified as responders (Dworaks tumor regression grade 3-4) and 36 patients (50%) achieved tumor down-staging. ROC analysis showed that both post-CRT SUV(max) and SRR were predictive factors for responders (p=0.03 and p=0.02, respectively). A threshold of post-CRT SUV(max) was 5.4 and that of SRR was 53.1%. Pre-CRT SUV(max), ΔSUV(max), and all parameters in regard to CEA were not significant in ROC analysis. CONCLUSIONS The post-CRT SUV(max) and SRR are potential factors for predicting tumor response in pre-operative CRT. The patients with lower post-CRT SUV(max) and higher SRR could be expected to achieve maximum tumor regression after pre-operative CRT in this study.

VEGF as a Predictor for Response to Definitive Chemoradiotherapy and COX-2 as a Prognosticator for Survival in Esophageal Squamous Cell Carcinoma

We investigated the patterns of pretreatment expression of the epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), and cyclooxygenase-2 (COX-2) by immunohistochemical staining and determined their correlation with treatment response and survival in 44 patients with esophageal squamous cell carcinoma (ESCC) treated with definitive concurrent chemoradiotherapy (CCRT). The definitive CCRT consisted of a median dose of 54 Gy (range: 40.0-68.4 Gy) and two cycles of concurrent administration of mostly 5-fluorouracil + cisplatinum. High expression of EGFR, VEGF, and COX-2 was found in 79.5%, 31.8%, and 38.6%, respectively. The Cox regression analysis for overall survival (OS) showed that both the treatment response and COX-2 expression were significant. The 3-yr OS rates of patients that achieved a complete response and those that did not were 46.7% and 5.3%, respectively (P = 0.006). The logistic regression analysis for treatment response with various parameters showed that only a high expression of VEGF was significantly associated with a complete response. Unlike other well-known studies, higher expression of VEGF was significantly correlated with a complete response to CCRT in this study. However, higher expression of COX-2 was significantly associated with shorter survival. These results suggest that VEGF might be a predictive factor for treatment response and COX-2 a prognostic factor for OS in patients with ESCC after definitive CCRT.

RESPIRATORY MOTIONAL EFFECT ON CONE-BEAM CT IN LUNG RADIATION SURGERY

The cone-beam CT (CBCT), which is acquired using an on-board imager (OBI) attached to a linear accelerator, is used effectively in the verification of setup accuracy for lung radiation surgery. In this study, the respiratory organ motional effect on the CBCT was evaluated with a properly devised phantom system, and the level of possible error in conditions of a real clinical process was assessed. In a comparison study between the CBCT in static status and CBCT images acquired in 20 different motional cases, we confirmed that the image quality and information of CBCT were degraded, with an increase of motional ranges in the region of inhomogeneous structures. The 4D-CT MIP (50 approximately 55%) for the planning of lung radiation surgery and the 4D-CT MIP (full phase) were compared with CBCT in the various motional cases for the evaluation of the influence of the motional effect on CBCT in the process of the setup error correction. The average ratio of relative difference between plan CT: 4D-CT MIP (50% approximately 55%) and CBCT was 5.79% and between plan CT: 4D-CT MIP (50% approximately 55%) and 4D-CT MIP (full phase) was 42.95% in the phantom study. In the analysis of clinical cases of lung radiation surgery, the gross tumor volumes were compared in each CT image. The average ratio of relative difference between plan CT: 4D-CT MIP (50 approximately 55%) and CBCT was 10.72% and between plan CT: 4D-CT MIP (50 approximately 55%) and 4D-CT MIP (full phase) was 28.19%. These results showed that, although a respiratory organ motional effect on CBCT introduced variation in image quality, the error as a result of this variation could be estimated relatively low in the setup error correction for a gated-lung radiation surgery when the planning was performed in 4D-CT MIP (50 approximately 55%), which already included a related signal of motional effect.

The Role of Radiotherapy in the Treatment of Gastric Mucosa-Associated Lymphoid Tissue Lymphoma

Purpose To assess radiotherapy for patients with early stage gastric mucosa-associated lymphoid tissue (MALT) lymphoma with respect to survival, treatment response, and complications. Materials and Methods Enrolled into this study were 48 patients diagnosed with gastric MALT lymphoma from January 2000 to September 2012. Forty-one patients had low grade and seven had mixed component with high grade. Helicobacter pylori eradication was performed in 33 patients. Thirty-four patients received radiotherapy alone. Ten patients received chemotherapy before radiotherapy, and three patients underwent surgery followed by chemotherapy and radiotherapy. One patient received surgery followed by radiotherapy. All patients received radiotherapy of median dose of 30.6 Gy. Results The duration of follow-up ranged from 6 to 158 months (median, 48 months). Five-year overall survival and cause-specific survival rates were 90.3% and 100%. All patients treated with radiotherapy alone achieved pathologic complete remission (pCR) in 31 of the low-grade and in three of the mixed-grade patients. All patients treated with chemotherapy and/or surgery prior to radiotherapy achieved pCR except one patient who received chemotherapy before radiotherapy. During the follow-up period, three patients developed diffuse large B-cell lymphoma in the stomach, and one developed gastric adenocarcinoma after radiotherapy. No grade 3 or higher acute or late complications developed. One patient, who initially exhibited gastroptosis, developed mild atrophy of left kidney. Conclusion These findings indicate that a modest dose of radiotherapy alone can achieve a high cure rate for low-grade and even mixed-grade gastric MALT lymphoma without serious toxicity. Patients should be carefully observed after radiotherapy to screen for secondary malignancies.

Concurrent chemoradiotherapy with cisplatin and fluorouracil for locally advanced hypopharyngeal carcinoma

Conclusions. The concurrent administration of cisplatin and fluorouracil (CCRT) during radiotherapy after induction chemotherapy had better results than induction chemotherapy followed by radiotherapy alone (CT+RT) for overall survival, laryngeal preservation, and locoregional control in patients with locally advanced hyopharyngeal cancer. Objectives. To report treatment results comparing CCRT with CT+RT in locally advanced hypopharyngeal cancer. Patients and methods. Sixty-six consecutive patients treated with curative intent were analyzed retrospectively. Thirty-eight patients were treated with induction chemotherapy followed by definitive RT, and 28 patients with induction chemotherapy followed by concurrent chemoradiotherapy. All patients had more than three cycles of continuous infusion of cisplatin and 5-fluorouracil every 3 weeks. The median dose of irradiation was 70 Gy in the CT+RT group and 68.4 Gy in the CCRT group, respectively. Results. The overall 5-year survival rates were 24% for the CT+RT group and 42% for the CCRT group (p=0.031). The 3-year pharyngolaryngectomy-free survival rates were 32% for the CT+RT group and 63% for the CCRT group (p=0.032). The 3-year locoregional control rate for CCRT was significantly better than that for the CT+RT (52% vs 23%, p=0.004). Acute hematologic toxicity appeared in 39% of the CT+RT patients and 75% of the CCRT patients.

Predictive factors for survival and correlation to toxicity in advanced Stage III non-small cell lung cancer patients with concurrent chemoradiation.

OBJECTIVE Concurrent chemoradiotherapy is the standard treatment for locally advanced Stage III non-small cell lung cancer in patients with a good performance status and minimal weight loss. This study aimed to define subgroups with different survival outcomes and identify correlations with the radiation-related toxicities. METHODS We retrospectively reviewed 381 locally advanced Stage III non-small cell lung cancer patients with a good performance status or weight loss of <10% who received concurrent chemoradiotherapy between 2004 and 2011. Three-dimensional conformal radiotherapy was administered once daily, combined with weekly chemotherapy. The Kaplan-Meier method was used for survival comparison and Cox regression for multivariate analysis. Multivariate analysis was performed using all variables with P values <0.1 from the univariate analysis. RESULTS Median survival of all patients was 24 months. Age > 75 years, the diffusion lung capacity for carbon monoxide ≤80%, gross tumor volume ≥100 cm(3) and subcarinal nodal involvement were the statistically significant predictive factors for poor overall survival both in univariate and multivariate analyses. Patients were classified into four groups according to these four predictive factors. The median survival times were 36, 29, 18 and 14 months in Groups I, II, III and IV, respectively (P < 0.001). Rates of esophageal or lung toxicity ≥Grade 3 were 5.9, 14.1, 12.5 and 22.2%, respectively. The radiotherapy interruption rate differed significantly between the prognostic subgroups; 8.8, 15.4, 22.7 and 30.6%, respectively (P = 0.017). CONCLUSION Severe toxicity and interruption of radiotherapy were more frequent in patients with multiple adverse predictive factors. To maintain the survival benefit in patients with concurrent chemoradiotherapy, strategies to reduce treatment-related toxicities need to be deeply considered.

Confidence limits for patient-specific IMRT dose QA: a multi-institutional study in Korea

This study aims to investigate tolerance levels for patient-specific IMRT dose QA (DQA) using the confidence limits (CL) determined by a multi-institutional study. Eleven institutions participated in the multi-institutional study in Korea. A total of 155 DQA measurements, consisting of point-dose differences (high- and low-dose regions) and gamma passing rates (composite and per-field) for IMRT patients with brain, head and neck (H&N), abdomen, and prostate cancers were examined. The Shapiro-Wilk test was used to evaluate the normality of data grouped by the treatment sites and the DQA methods. The confidence limit coefficients in cases of the normal distribution, and the two-sided Students t-distribution were applied to determine the confidence limits for the grouped data. The Spearmans test was applied to assess the sensitivity of DQA results within the limited groups. The differences in CLs between the two confidence coefficients based on the normal and t-distributions were negligible for the point-dose data and the gamma passing rates with 3%/3 criteria. However, with 2%/2 criteria, the difference in CLs were 1.6% and 2.2% for composite and per-field measurements, respectively. This resulted from the large standard deviation and the more sensitive criteria of 2%/2. There was no noticeable correlation among the different QA methods. Our multi-institutional study suggested that the CL was not a suitable metric for defining the tolerance level when the statistics of the sample group did not follow the normality and had a large standard deviation. PACS number: 87.55.Qr.This study aims to investigate tolerance levels for patient‐specific IMRT dose QA (DQA) using the confidence limits (CL) determined by a multi‐institutional study. Eleven institutions participated in the multi‐institutional study in Korea. A total of 155 DQA measurements, consisting of point‐dose differences (high‐ and low‐dose regions) and gamma passing rates (composite and per‐field) for IMRT patients with brain, head and neck (H&N), abdomen, and prostate cancers were examined. The Shapiro‐Wilk test was used to evaluate the normality of data grouped by the treatment sites and the DQA methods. The confidence limit coefficients in cases of the normal distribution, and the two‐sided Students t‐distribution were applied to determine the confidence limits for the grouped data. The Spearmans test was applied to assess the sensitivity of DQA results within the limited groups. The differences in CLs between the two confidence coefficients based on the normal and t‐distributions were negligible for the point‐dose data and the gamma passing rates with 3%/3 criteria. However, with 2%/2 criteria, the difference in CLs were 1.6% and 2.2% for composite and per‐field measurements, respectively. This resulted from the large standard deviation and the more sensitive criteria of 2%/2. There was no noticeable correlation among the different QA methods. Our multi‐institutional study suggested that the CL was not a suitable metric for defining the tolerance level when the statistics of the sample group did not follow the normality and had a large standard deviation. PACS number: 87.55.Qr

Effect of irradiation-induced intercellular adhesion molecule-1 expression on natural killer cell-mediated cytotoxicity toward human cancer cells

BACKGROUND AIMS Irradiation enhances the adhesion between natural killer (NK) cells and target cells by up-regulating intercellular adhesion molecule-1 (ICAM-1) on target cells. Therefore, we investigated the effect of irradiation-induced ICAM-1 expression on human cancer cells on NK cell-mediated cytotoxicity. METHODS Expression levels of ICAM-1 on the target cell surface before and after irradiation of six human cancer cell lines (HL60, SKBR-3, T47D, HCT-116, U937 and U251) were analyzed by flow cytometry. Ex vivo expansion of NK cells from human peripheral blood mononuclear cells was performed by co-culture with irradiated K562 cells. The related adhesion molecule lymphocyte function-associated antigen 1 (LFA-1) on NK cells was analyzed by flow cytometry. An enzyme-linked immunosorbent assay was used to detect interferon-γ (IFN-γ), and WST-8 assays were performed to check NK cell cytotoxicity. Finally, blocking assays were performed using monoclonal antibodies against ICAM-1 or LFA-1. RESULTS LFA-1 expression increased on NK cells after expansion (P <0.001). The expression of ICAM-1 was significantly upregulated by irradiation after 24 h in various cell lines, including HL60 (P <0.001), SKBR-3 (P <0.001), T47D (P <0.001) and U937 (P <0.001), although the level of expression depended on the cell line. ICAM-1 expression was extremely low before and after irradiation in U251 cells. NK cell-mediated cytotoxicity increased after irradiation of HL60 (P <0.001), SKBR-3 (P <0.001), T47D (P = 0.003), and U937 (P = 0.004) cells, in which ICAM-1 expression was significantly increased after irradiation. IFN-γ production by NK cells in response to HL60 (P <0.001) and T47D (P = 0.011) cells significantly increased after irradiation. NK cell-mediated cytotoxicity against irradiated SKBR-3 (P <0.001) and irradiated T47D cells (P = 0.035) significantly decreased after blocking of ICAM-1. Blocking of LFA-1 on NK cells resulted in reduced cytotoxicity against irradiated HL60 (P <0.001) and irradiated SKBR-3 (P <0.001). CONCLUSIONS Irradiation upregulates ICAM-1 expression on the surface of human cancer cells and enhances activated NK cell-mediated cytotoxicity. Therefore, irradiation combined with NK cell therapy may improve the antitumor effects of NK cells.

Effect of image value-to-density table (IVDT) on the accuracy of delivery quality assurance (DQA) process in helical tomotherapy

The effect of the accuracy in the application of the image value-to-density table (IVDT) from kilovoltage computed tomography (kVCT) and mega-voltage computed tomography (MVCT) images on the delivery quality assurance (DQA) in helical tomotherapy (HT) was analyzed. The DQA plans were prepared with a kVCT image of a cheese phantom for 10 HT patients, and the difference in absolute dose equivalence between the planned and real measurement was evaluated according to the accuracy of IVDT application. The difference between the calculated dose distribution and real dose distribution measured with MapCHECK (SunNuclear, Melbourne, FL) was analyzed through the DQA process with a kVCT MapCHECK image and the same analysis was performed with an MVCT MapCHECK image. The IVDT for kVCT was applied to MVCT and the variation in error between the planned and real measurement caused by improper application of IVDT was evaluated. The accuracy of the IVDT application in the homogeneous water-equivalent cheese phantom had only a minor influence on the dose calculation. Although the overall accuracy of the calculated dose was increased when the proper IVDT was applied, this result had no statistical significance. The MVCT image of MapCHECK contained less error between the calculated dose and delivered dose with a high pass rate. The proper IVDT application to the MVCT image of MapCHECK increased the accuracy of dose calculation, and this result had a statistical significance. Application of the correct IVDT is important in HT DQA and its significance is increased when using phantoms consisting of inhomogeneous density materials.