• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.5625-5633
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• 2015

Background: ${\beta}$-catenin plays a crucial role in the progression of breast cancer (BC) and a prognostic role of in BC patients has been widely reported. However, controversy still remains. Materials and Methods: Identical search strategies were used to search relevant literature in electronic databases updated to July 1, 2014. Individual hazard ratios (HRs) and 95% confidence intervals (CIs) were extracted and pooled HRs with 95%CIs were used to evaluate the strength of association between positive ${\beta}$-catenin expression in different subcellular locations and survival results of BC patients. Subgroup and meta-regression analyses were performed to explore heterogeneity. Funnel plots of Begg's and Egger's linear regression test were used to investigate publication bias. Heterogeneity and sensitivity were also assessed. All the work was completed using STATA. Results: A total of 2,204 patients from 12 evaluative studies were finally included. Pooled HRs and 95%CIs suggested that ${\beta}$-catenin expression in cytoplasm/nucleus had an unfavorable impact on both overall survival (OS) (HR: 1.93, 95%CI: 1.40-2.65) and disease free survival (DFS)/ recurrent free survival (RFS) (HR: 1.60, 95%CI: 1.20-2.13) in BC patients. However, here was no significant association between ${\beta}$-catenin expression in the membranes with OS (HR: 0.65, 95%CI: 0.42-1.02) or DFS/RFS (HR: 0.66, 95%CI: 0.38-1.13). Publication bias was absent in all of the four outcomes. Sensitivity analysis revealed that the results of this meta-analysis were robust. Conclusions: Positive ${\beta}$-catenin expression in cytoplasm/nucleus rather than in membrane is a significant prognostic factor in patients with BC who have been surgically treated.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.2851-2857
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• 2013

Objective: REPS2 plays important roles in inhibiting cell proliferation, migration and in inducing apoptosis of cancer cells, now being identified as a useful biomarker for favorable prognosis in prostate and breast cancers. The purpose of this study was to assess REPS2 expression and to explore its role in esophageal squamous cell carcinoma (ESCC). Methods: Protein expression of REPS2 in ESCCs and adjacent non-cancerous tissues from 120 patients was analyzed by immunohistochemistry and correlated with clinicopathological parameters and patient outcome. Additionally, thirty paired ESCC tissues and four ESCC cell lines and one normal human esophageal epithelial cell line were evaluated for REPS2 mRNA and protein expression levels by quantitative RT-PCR and Western blotting. Results: REPS2 mRNA and protein expression levels were down-regulated in ESCC tissues and cell lines. Low protein levels were significantly associated with primary tumour, TNM stage, lymph node metastasis and recurrence (all, P < 0.05). Survival analysis demonstrated that decreased REPS2 expression was significantly associated with shorter overall survival and disease-free survival (both, P < 0.001), especially in early stage ESCC patients. When REPS2 expression and lymph node metastasis status were combined, patients with low REPS2 expression/lymph node (+) had both poorer overall and disease-free survival than others (both, P < 0.001). Cox multivariate regression analysis further revealed REPS2 to be an independent prognostic factor for ESCC patients. Conclusions: Our findings demonstrate that downregulation of REPS2 may contribute to malignant progression of ESCC and represent a novel prognostic marker and a potential therapeutic target for ESCC patients.

• Radiation Oncology Journal
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• v.37 no.3
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• pp.156-165
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• 2019

Purpose: Prophylactic cranial irradiation (PCI) is a standard treatment for limited-stage small cell lung cancer (LS-SCLC) showing a response to initial treatment, but many patients do not receive PCI due to comorbidities or refusal. This study aims to define the patient group for whom PCI can be omitted with minimal risk. Materials and Methods: Patients with LS-SCLC who underwent radiotherapy with curative aim at our institution between January 2004 and December 2015 were retrospectively reviewed. Patients who did not receive PCI were evaluated for brain metastasis-free survival (BMFS), progression-free survival (PFS), overall survival (OS), and prognostic factors for survival, and treatment outcomes were compared with a patient cohort who received PCI. Results: A total of 350 patients achieved a response following thoracic radiotherapy, and 190 of these patients did not receive PCI. Stage I-II and a complete response (CR) to initial therapy were good prognostic factors for BMFS and OS on univariate analysis. Patients with both stage I-II and a CR who declined PCI showed comparable 2-year BMFS to those who received PCI (92% vs. 89%). In patients who achieved CR, PCI did not significantly improve OS or PFS. Conclusion: There should be less concern about omitting PCI in patients with comorbidities if they have stage I-II or a CR, with brain metastasis control being comparable to those patients who receive PCI.

• Radiation Oncology Journal
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• v.31 no.1
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• pp.18-24
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• 2013

Purpose: The purpose of this study was to assess the clinical outcomes of hypofractionated radiotherapy (HFRT) with three-dimensional conformal technique for medically inoperable patients with early stage non-small-cell lung cancer (NSCLC) and to evaluate prognostic factors. Materials and Methods: We performed a retrospective review of 26 patients who underwent HFRT for early stage NSCLC between September 2005 and August 2011. Only clinical stage T1-3N0 was included. The median RT dose was 70 Gy (range, 60 to 72 Gy) and the median biologically equivalent dose (BED) was 94.5 Gy (range, 78.0 to 100.8 Gy). In 84.6% of patients, 4 Gy per fraction was used. Neoadjuvant chemotherapy with paclitaxel and cisplatin was given to 2 of 26 patients. Results: The median follow-up time for surviving patients was 21 months (range, 13 to 49 months). The overall response rate was 53.9%, and the initial local control rate was 100%. The median survival duration was 27.8 months. Rates of 2-year overall survival, progression-free survival (PFS), local control (LC), and locoregional-free survival (LRFS) were 54.3%, 61.1%, 74.6%, and 61.9%, respectively. Multivariate analysis showed that BED (>90 vs. ${\leq}90$ Gy) was an independent prognostic factor influencing PFS, LC, and LRFS. Severe toxicities over grade 3 were not observed. Conclusion: Radical HFRT can yield satisfactory disease control with acceptable rates of toxicities in medically inoperable patients with early stage NSCLC. HFRT is a viable alternative for clinics and patients ineligible for stereotactic ablative radiotherapy. BED over 90 Gy and 4 Gy per fraction might be appropriate for HFRT.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.7
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• pp.4255-4259
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• 2013

Background: Soft tissue sarcomas (STS) are a heterogeneous group of tumors, and approximately 40-50% of patients with STS develop metastatic disease. The median overall survival of those patients was 12 months and their 5-year survival rate was 8%. Therefore, study on more effective treatment, especially the targeting therapies, is urgently needed. Objective: To evaluate the efficacy and safety of Endostar$^{(R)}$ combined with chemotherapy in patients with advanced STS. Methods: A retrospective case-series study was conducted in Cancer Institute of PLA, Xinqiao Hospital. A total of 71 patients suffering from advanced STS (IIB - IV) were included, of whom 49 cases treated with chemotherapy alone were defined as the control group and the rest 22 cases treated with the traditional chemotherapy combined with Endostar$^{(R)}$ were defined as the test group. The short-term therapeutic effects including objective response rate (ORR), disease control rate (DCR) and safety were evaluated in the two groups. In the follow-up, progression-free survival (PFS) and overall survival (OS) were also observed. Results: In the test and control groups, the ORR was 18.2% and 12.2%, respectively (P=0.767), and the DCR was 86.4% and 61.2%, respectively (P=0.034). The median time to progression in the test and control groups was 120 days and 70 days with significant difference (P = 0.017), while the median overall survival was 452 days and 286 days without significant difference (P=0.503). The one-year survival rate in the test group and control group was 56.2% and 35.4%, respectively, while the two-year survival rate was 30.2% and 26.5%, respectively. No significant difference in the side effects was found between the two groups. Conclusions: Endostar$^{(R)}$ combined with chemotherapy resulted in a higher DCR and longer PFS in the patients with advanced STS, and the toxicity was tolerable.

• Journal of Korean Neurosurgical Society
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• v.64 no.2
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• pp.271-281
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• 2021

Objective : Immune checkpoint inhibitors (ICIs) are approved for treating non-small-cell lung cancer (NSCLC); however, the safety and efficacy of combined ICI and Gamma Knife radiosurgery (GKS) treatment remain undefined. In this study, we retrospectively analyzed patients treated with ICIs with or without GKS at our institute to manage patients with brain metastases from NSCLC. Methods : We retrospectively reviewed medical records of patients with brain metastases from NSCLC treated with ICIs between January 2015 and December 2017. Of 134 patients, 77 were assessable for brain responses and categorized into three groups as follows : group A, ICI alone (n=26); group B, ICI with concurrent GKS within 14 days (n=24); and group C, ICI with non-concurrent GKS (n=27). Results : The median follow-up duration after brain metastasis diagnosis was 19.1 months (range, 1-77). At the last follow-up, 53 patients (68.8%) died, 20 were alive, and four were lost to follow-up. The estimated median overall survival (OS) of all patients from the date of brain metastasis diagnosis was 20.0 months (95% confidence interval, 12.5-27.7) (10.0, 22.5, and 42.1 months in groups A, B, and C, respectively). The OS was shorter in group A than in group C (p=0.001). The intracranial disease progression-free survival (p=0.569), local progression-free survival (p=0.457), and complication rates did not significantly differ among the groups. Twelve patients showed leptomeningeal seeding (LMS) during follow-up. The 1-year LMS-free rate in treated with ICI alone group (69.1%) was significantly lower than that in treated with GKS before ICI treatment or within 14 days group (93.2%) (p=0.004). Conclusion : GKS with ICI showed no favorable OS outcome in treating brain metastasis from NSCLC. However, GKS with ICI did not increase the risk of complications. Furthermore, compared with ICI alone, GKS with ICI may be associated with a reduced incidence of LMS. Further understanding of the mechanism, which remains unknown, may help improve the quality of life of patients with brain metastasis.

• Journal of Gastric Cancer
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• v.17 no.1
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• pp.21-32
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• 2017

Purpose: Perioperative chemotherapy improves survival outcomes in locally advanced (LA) gastric cancer. Materials and Methods: We retrospectively analyzed patients with LA gastric cancer who were offered perioperative chemotherapy consisting of epirubicin, oxaliplatin, and capecitabine (EOX) from May 2013 to December 2015 at Tata Memorial Hospital in Mumbai. Results: Among the 268 consecutive patients in our study, 260 patients (97.0%) completed neoadjuvant chemotherapy, 200 patients (74.6%) underwent D2 lymphadenectomy, and 178 patients (66.4%) completed adjuvant chemotherapy. The median follow-up period was 17 months. For the entire cohort, the median overall survival (OS), 3-year OS rate, median progression-free survival (PFS), and 3-year PFS rate were 37 months, 64.4%, 31 months, and 40%, respectively. PFS and OS were significantly inferior in patients who presented with features of obstruction than in those who did not (P=0.0001). There was no difference in survival with respect to tumor histology (well to moderately differentiated vs. poorly differentiated, signet ring vs. non-signet ring histology) or location (proximal vs. distal). Survival was prolonged in patients with an early pathological T stage and a pathological node-negative status. In a multivariate analysis, postoperative pathological nodal status and gastric outlet obstruction on presentation significantly correlated with survival. Conclusions: EOX chemotherapy with curative resection and D2 lymphadenectomy is a suggested alternative to the existing perioperative regimens. The acceptable postoperative complication rate and relatively high resections, chemotherapy completion, and survival rates obtained in this study require further evaluation and validation in a clinical trial.

• Radiation Oncology Journal
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• v.25 no.3
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• pp.170-176
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• 2007

Purpose: To determine the role of radiotherapy for the treatment of portal vein thrombosis (PVT) from hepatocellular carcinoma (HCC). Material and Methods: A retrospective analysis was performed on 70 patients that had been diagnosed with HCC and were treated with three-dimensional conformal radiotherapy (3D-CRT) for the PVT. The radiation dose ranged from 40 Gy to 60 Gy (median dose: 48 Gy) and the biological effective dose (BED) ranged from 31.3 Gy to 78.0 $Gy_{10}$ (median dose: 61.6 $Gy_{10}$). Response was determined by measuring the extent of the PVT on a CT image at 0, 1 and 3 months after completion of the radiotherapy. The median follow-up period was 9 months. Results: The response rate was 47.1% (33 patients), with two patients (2.9%) showing a complete response, 31 patients (44.3%) showing a partial response, and 35 patients (50%) showing stable disease or no response. The 1-year progression-free survival rate was 60%, and the median progression-free survival time was 17 months. The median overall survival time was 11 months, the median survival time in the responders was 15 months and in the nonresponders was 8 months (p=0.032). Four patients (5.7%) had transient liver function impairment during treatment. Radiation induced liver disease (RILD) was observed in only one patient (1.4%). Conclusion: Three-dimensional conformal radiotherapy for the treatment of PVT from advanced HCC was a relatively effective and safe method.

• Tuberculosis and Respiratory Diseases
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• v.61 no.2
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• pp.143-149
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• 2006

Background: Irinotecan (topoisomerase I inhibitor) is effective as a monotherapy against small-cell lung cancer(SCLC). Cisplatin is also an important drug against SCLC. A phase II study of irinotecan combined with cisplatin was carried out to evaluate the efficacy and toxicity of this combined regimen as a first line treatment in patients with extensive SCLC. Methods: Thirty-nine patients with previously untreated extensive SCLC were enrolled in this study. Irinotecan $60mg/m^2$ was administered intravenously on days 1, 8 and 15, and in combination with cisplatin $60mg/m^2$ on day 1 and every 28 days thereafter. Four cycles of chemotherapy were given to the patients. Results: The overall response rate was 77% with a complete response (CR) rate of 8%. The median survival time, 1- and 2-year survival rate were 14.8 months, 60.9% and 27.6%, respectively. The median progression free survival time, 6-and 12-month progression free survival rate were 8.4 months, 75% and 18.8%, respectively. The WHO grade 3 or more toxicity encountered were leukopenia (23%), diarrhea (26%). Two patients changed their chemotherapeutic regimen and one patient died from severe diarrhea. Conclusion: The combination of irinotecan and cisplatin is effective as a first line therapy in extensive SCLC is effective, but has severe or fatal diarrhea as toxicity.

• Radiation Oncology Journal
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• v.36 no.2
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• pp.103-113
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• 2018

Purpose: Anaplastic thyroid cancer (ATC) is a rare tumor with a lethal clinical course despite aggressive multimodal therapy. Intensity-modulated radiotherapy (IMRT) may achieve a good therapeutic outcome in ATC patients, and the role of IMRT should be assessed. We retrospectively reviewed outcomes for ATC treated with three-dimensional conformal radiotherapy (3D-CRT) or IMRT to determine the optimal treatment option and explore the role of radiotherapy (RT). Materials and Methods: Between December 2000 and December 2015, 41 patients with pathologically proven ATC received RT with a sufficient dose of ${\geq}40Gy$. Among them, 21 patients (51%) underwent surgery before RT. Twenty-eight patients received IMRT, and 13 received 3D-CRT. Overall survival (OS) and progression-free survival (PFS), patterns of failure, and toxicity were examined. Results: The median follow-up time for survivors was 38.0 months. The median and 1-year OS and PFS rates were 7.2 months and 29%, 4.5 months and 15%, respectively. Surgery significantly improved the prognosis (median OS: 10.7 vs. 3.9 months, p = 0.001; median PFS: 5.9 vs. 2.5 months, p = 0.007). IMRT showed significantly better PFS and OS than 3D-CRT, even in multivariate analysis (OS: hazard ratio [HR] = 0.30, p = 0.005; PFS: HR = 0.33, p = 0.005). Significantly higher radiation dose could be delivered with IMRT than 3D-CRT ($EQD2_{10}$ 66 vs. 60 Gy, p = 0.005). Only 2 patients had grade III dermatitis after IMRT. No other severe toxicity ${\geq}grade$ III occurred. Conclusion: Patients with ATC showed better prognosis through multimodal treatment. Furthermore, IMRT could achieve favorable survival rates by safely delivering higher dose than 3D-CRT.