Bae Kwon Jeong

The prognostic impact of the neutrophil-to-lymphocyte ratio in patients with small-cell lung cancer.

Background:The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are prognostic factors for various types of cancer. In this study, we assessed the association of NLR and PLR with the prognosis of small-cell lung cancer (SCLC) in patients who received the standard treatment.Methods:We retrospectively reviewed patients who were diagnosed with SCLC and treated with platinum-based chemotherapy between July 2006 and October 2013 in Gyeongsang National University Hospital Regional Cancer Center and Changwon Samsung Hospital.Results:In total, 187 patients were evaluated. Compared with low NLR (<4), high NLR (⩾4) at diagnosis was associated with poor performance status, advanced stage, and lower response rate. Median overall survival (OS) and progression-free survival (PFS) were worse in the high-NLR group (high vs low, 11.17 vs 9.20 months, P=0.019 and 6.90 vs 5.49 months, P=0.005, respectively). In contrast, PLR at diagnosis was not associated with OS or PFS (P=0.467 and P=0.205, respectively). In multivariate analysis, stage, lactate dehydrogenase, and NLR at diagnosis were independent prognostic factors for OS and PFS.Conclusions:NLR is easily measurable and reflects the SCLC prognosis. A future prospective study is warranted to confirm our results.

Concurrent chemoradiotherapy for elderly patients with stage III non-small cell lung cancer

Purpose Combined chemoradiotherapy is standard management for locally advanced non-small cell lung cancer (LA-NSCLC), but standard treatment for elderly patients with LA-NSCLC has not been confirmed yet. We evaluated the feasibility and efficacy of concurrent chemoradiotherapy (CCRT) for elderly patients with LA-NSCLC. Materials and Methods Among patients older than 65 years with LA-NSCLC, 36 patients, who underwent CCRT were retrospectively analyzed. Chemotherapy was administered 3-5 times with 4 weeks interval during radiotherapy. Thoracic radiotherapy was delivered to the primary mass and regional lymph nodes. Total dose of 54-59.4 Gy (median, 59.4 Gy) in daily 1.8 Gy fractions and 5 fractions per week. Results Regarding the response to treatment, complete response, partial response, and no response were shown in 16.7%, 66.7%, and 13.9%, respectively. The 1- and 2-year overall survival (OS) rates were 58.2% and 31.2%, respectively, and the median survival was 15 months. The 1- and 2-year progression-free survivals (PFS) were 41.2% and 19.5%, respectively, and the median PFS was 10 months. Regarding to the toxicity developed after CCRT, pneumonitis and esophagitis with grade 3 or higher were observed in 13.9% (5 patients) and 11.1% (4 patients), respectively. Treatment-related death was not observed. Conclusion The treatment-related toxicity as esophagitis and pneumonitis were noticeably lower when was compared with the previously reported results, and the survival rate was higher than radiotherapy alone. The results indicate that CCRT is an effective in terms of survival and treatment related toxicity for elderly patients over 65 years old with LA-NSCLC.

Prognostic value of different patterns of squamous cell carcinoma antigen level for the recurrent cervical cancer.

PURPOSE In some unusual cases, in patients with cervical cancer, an elevation of squamous cell carcinoma antigen (SCC-Ag) was not observed at diagnosis but was observed on recurrence, or vice versa. The objective of this study was to identify patient-, disease-, and treatment-related factors associated with this unusual level of SCC-Ag, and to determine whether SCC-Ag is a useful tumor marker in such patients. MATERIALS AND METHODS Among 129 patients with recurrence, 14 who showed a normal SCC-Ag level at diagnosis but an elevated level at recurrence were classified as group I; 22 patients with an elevated SCC-Ag level at diagnosis but not at recurrence were classified as group II; and 76 patients with an elevated SCC-Ag level at both diagnosis and recurrence were classified as group III. RESULTS In univariate analysis, unusual SCC-Ag showed statistically significant relationships with pathology and biochemical response to treatment. However, in the multivariate analysis, none of the clinicopathologic factors showed a statistical relationship with unusual levels of SCC-Ag. The 5-year disease-free survival rates for groups I, II, and III were 7.1%, 9.1%, and 0% (p=0.418), and the 5-year overall survival rates were 34.3%, 58.4%, and 33.3% (p=0.142), respectively. CONCLUSION The value of SCC-Ag has been confirmed in all patients; thus, check of SCC-Ag level at follow-up should be considered. Although no statistically significant differences were observed among the groups, we conclude that patients with a high initial SCC-Ag and elevated SCC-Ag at relapse have poor prognosis due to high SCC-Ag level.

Effect of early chemoradiotherapy in patients with limited stage small cell lung cancer

Purpose We evaluated the effect of early chemoradiotherapy on the treatment of patients with limited stage small cell lung cancer (LS-SCLC). Materials and Methods Between January 2006 and December 2011, thirty-one patients with histologically proven LS-SCLC who were treated with two cycles of chemotherapy followed by concurrent chemoradiotherapy and consolidation chemotherapy were retrospectively analyzed. The chemotherapy regimen was composed of etoposide and cisplatin. Thoracic radiotherapy consisted of 50 to 60 Gy (median, 54 Gy) given in 5 to 6.5 weeks. Results The follow-up period ranged from 5 to 53 months (median, 22 months). After chemoradiotherapy, 35.5% of the patients (11 patients) showed complete response, 61.3% (19 patients) showed partial response, 3.2% (one patient) showed progressive disease, resulting in an overall response rate of 96.8% (30 patients). The 1-, 2-, and 3-year overall survival (OS) rates were 66.5%, 41.0%, and 28.1%, respectively, with a median OS of 21.3 months. The 1-, 2-, and 3-year progression free survival (PFS) rates were 49.8%, 22.8%, and 13.7%, respectively, with median PFS of 12 months. The patterns of failure were: locoregional recurrences in 29.0% (nine patients), distant metastasis in 9.7% (three patients), and both locoregional and distant metastasis in 9.7% (three patients). Grade 3 or 4 toxicities of leukopenia, anemia, and thrombocytopenia were observed in 32.2%, 29.0%, and 25.8%, respectively. Grade 3 radiation esophagitis and radiation pneumonitis were shown in 12.9% and 6.4%, respectively. Conclusion We conclude that early chemoradiotherapy for LS-SCLC provides feasible and acceptable local control and safety.

Effect of alpha-lipoic acid on radiation-induced small intestine injury in mice

Purpose Radiation therapy is a highly effective treatment for patients with solid tumors. However, it can cause damage and inflammation in normal tissues. Here, we investigated the effects of alpha-lipoic acid (ALA) as radioprotection agent for the small intestine in a mouse model. Materials and Methods Whole abdomen was evenly irradiated with total a dose of 15 Gy. Mice were treated with either ALA (100 mg/kg, intraperitoneal injection [i.p.]) or saline (equal volume, i.p.) the prior to radiation as 100 mg/kg/day for 3 days. Body weight, food intake, histopathology, and biochemical parameters were evaluated. Results Significant differences in body weight and food intake were observed between the radiation (RT) and ALA + RT groups. Moreover, the number of crypt cells was higher in the ALA + RT group. Inflammation was decreased and recovery time was shortened in the ALA + RT group compared with the RT group. The levels of inflammation-related factors (i.e., phosphorylated nuclear factor kappa B and matrix metalloproteinase-9) and mitogen-activated protein kinases were significantly decreased in the ALA + RT group compared with those in the RT group. Conclusions ALA treatment prior to radiation decreases the severity and duration of radiation-induced enteritis by reducing inflammation, oxidative stress, and cell death.

Combination effects of tissue heterogeneity and geometric targeting error in stereotactic body radiotherapy for lung cancer using CyberKnife

We have investigated the combined effect of tissue heterogeneity and its variation associated with geometric error in stereotactic body radiotherapy (SBRT) for lung cancer. The treatment plans for eight lung cancer patients were calculated using effective path length (EPL) correction and Monte Carlo (MC) algorithms, with both having the same beam configuration for each patient. These two kinds of plans for individual patients were then subsequently recalculated with adding systematic and random geometric errors. In the ordinary treatment plans calculated with no geometric offset, the EPL calculations, compared with the MC calculations, largely overestimated the doses to PTV by ∼21%, whereas the overestimation were markedly lower in GTV by ∼12% due to relatively higher density of GTV than of PTV. When recalculating the plans for individual patients with assigning the systematic and random geometric errors, no significant changes in the relative dose distribution, except for overall shift, were observed in the EPL calculations, whereas largely altered in the MC calculations with a consistent increase in dose to GTV. Considering the better accuracy of MC than EPL algorithms, the present results demonstrated the strong coupling of tissue heterogeneity and geometric error, thereby emphasizing the essential need for simultaneous correction for tissue heterogeneity and geometric targeting error in SBRT of lung cancer. PACS numbers: 87.55.D, 87.55.kh, 87.53.Ly, 87.55.‐xWe have investigated the combined effect of tissue heterogeneity and its variation associated with geometric error in stereotactic body radiotherapy (SBRT) for lung cancer. The treatment plans for eight lung cancer patients were calculated using effective path length (EPL) correction and Monte Carlo (MC) algorithms, with both having the same beam configuration for each patient. These two kinds of plans for individual patients were then subsequently recalculated with adding systematic and random geometric errors. In the ordinary treatment plans calculated with no geometric offset, the EPL calculations, compared with the MC calculations, largely overestimated the doses to PTV by ∼21%, whereas the overestimation were markedly lower in GTV by ∼12% due to relatively higher density of GTV than of PTV. When recalculating the plans for individual patients with assigning the systematic and random geometric errors, no significant changes in the relative dose distribution, except for overall shift, were observed in the EPL calculations, whereas largely altered in the MC calculations with a consistent increase in dose to GTV. Considering the better accuracy of MC than EPL algorithms, the present results demonstrated the strong coupling of tissue heterogeneity and geometric error, thereby emphasizing the essential need for simultaneous correction for tissue heterogeneity and geometric targeting error in SBRT of lung cancer. PACS numbers: 87.55.D, 87.55.kh, 87.53.Ly, 87.55.-x.

HIF-1α and CA-IX as predictors of locoregional control for determining the optimal treatment modality for early-stage laryngeal carcinoma.

The purpose of this study was to examine the predictive value of hypoxia‐inducible factor (HIF)−1α, carbonic anhydrase (CA)‐IX, glucose transporter (GLUT)−1, cyclooxygenase (COX)−2, Ki‐67, and erythropoietin receptor (EPOR) as immunohistochemical markers for determining the optimal treatment modality for early stage laryngeal carcinoma.

Alpha lipoic acid attenuates radiation-induced thyroid injury in rats.

Exposure of the thyroid to radiation during radiotherapy of the head and neck is often unavoidable. The present study aimed to investigate the protective effect of α-lipoic acid (ALA) on radiation-induced thyroid injury in rats. Rats were randomly assigned to four groups: healthy controls (CTL), irradiated (RT), received ALA before irradiation (ALA + RT), and received ALA only (ALA, 100 mg/kg, i.p.). ALA was treated at 24 h and 30 minutes prior to irradiation. The neck area including the thyroid gland was evenly irradiated with 2 Gy per minute (total dose of 18 Gy) using a photon 6-MV linear accelerator. Greater numbers of abnormal and unusually small follicles in the irradiated thyroid tissues were observed compared to the controls and the ALA group on days 4 and 7 after irradiation. However, all pathologies were decreased by ALA pretreatment. The quantity of small follicles in the irradiated rats was greater on day 7 than day 4 after irradiation. However, in the ALA-treated irradiated rats, the numbers of small and medium follicles were significantly decreased to a similar degree as in the control and ALA-only groups. The PAS-positive density of the colloid in RT group was decreased significantly compared with all other groups and reversed by ALA pretreatment. The high activity index in the irradiated rats was lowered by ALA treatment. TGF-ß1 immunoreactivity was enhanced in irradiated rats and was more severe on the day 7 after radiation exposure than on day 4. Expression of TGF-ß1 was reduced in the thyroid that had undergone ALA pretreatment. Levels of serum pro-inflammatory cytokines (TNF-α, IL-1ß and IL-6) did not differ significantly between the all groups. This study provides that pretreatment with ALA decreased the severity of radiation-induced thyroid injury by reducing inflammation and fibrotic infiltration and lowering the activity index. Thus, ALA could be used to ameliorate radiation-induced thyroid injury.

Defining Radiation-Induced Hepatic Toxicity in Hepatocellular Carcinoma Patients Treated with Stereotactic Body Radiotherapy

The definition and criteria of radiation-induced hepatic toxicity (RIHT) in hepatocellular carcinoma patients vary among studies. Therefore, the reported rates of RIHT differ among studies, and this causes confusion. In this study, we evaluated RIHT using several laboratory and clinical parameters, and analyzed which criterion is more correlated with RT and survival. Forty-five HCC patients treated with stereotactic body radiotherapy were included for the analysis. All patients had unresectable HCC and Child-Pugh (CP) class A or B baseline liver function. A median total dose of 45 Gy was delivered by CyberKnife in 3 fractions. For individual laboratory parameter, ≥ grade 2 toxicity development of bilirubin, albumin, or prothrombin time by Common Terminology Criteria of Adverse Effects (CTCAE) was correlated with mean liver dose and survival. However, serum transaminases had no correlation with liver mean dose and survival, and were rather affected by other local treatments. Compared to the CTCAE, the increase in the CP score of 2 points or more was better correlated with liver failure and overall survival, and it was not affected by other local treatments or tumor progression. We concluded RIHT was better defined by the change in the CP score rather than the CTCAE in patients treated by stereotactic body radiotherapy for HCC.

Stereotactic Body Radiation Therapy for Low- to Intermediate-risk Prostate Adenocarcinoma.

The aim of the present study was to evaluate the efficacy and toxicity of stereotactic body radiation therapy (SBRT) for low- to intermediate-risk prostate adenocarcinoma. Thirty-nine patients were retrospectively reviewed. The SBRT was delivered using the CyberKnife with the fiducial tracking method combined with In-tempo imaging. The gross target volume, which included the prostate only, was delineated on the fused CT/MRI scans. The prescription dose was delivered every other day as 5 fractions of 7.5 Gy. Venous blood was obtained before and after SBRT to assess the prostate-specific antigen (PSA) level. Toxicity was evaluated using the CTCAE, v4.03. The median follow-up time was 30.0 months. The median initial PSA level was 7.7 ng/mL. PSA levels decreased in all patients treated with SBRT, and after 5 months, the median PSA was less than 2 ng/mL. The rate of overall 3-yr actuarial biochemical failure free survival was 93.9%. Acute side effects were generally comparable with those of previous studies. The PSA change and toxicity after SBRT for low- to intermediate-risk prostate adenocarcinoma indicates favorable biochemical responses and tolerable levels of toxicity. Additionally short course treatment may produce cost benefit and convenience to patients.