• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.5699-5703
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• 2013

Objective: To investigate the clinical effects of whole brain radiotherapy concomitant with targeted therapy for brain metastasis in non-small cell lung cancer (NSCLC) patients with chemotherapy failure. Materials and Methods: Of the 157 NSCLC patients with chemotherapy failure followed by brain metastasis admitted in our hospital from January 2009 to August 2012, the combination group (65 cases) were treated with EGFR-TKI combined with whole brain radiotherapy while the radiotherapy group (92 cases) were given whole brain radiotherapy only. Short-term effects were evaluated based on the increased MRI in brain 1 month after whole brain radiotherapy. Intracranial hypertension responses, hematological toxicity reactions and clinical effects of both groups were observed. Results: There were more adverse reactions in the combination group than in radiotherapy group, but no significant differences were observed between the two groups in response rate (RR) and disease control rate (DCR) (P>0.05). Medium progression free survival (PFS), medium overall survival (OS) and 1-year survival rate in combination group were 6.0 months, 10.6 months and 42.3%, while in the radiotherapy group they were 3.4 months, 7.7 months and 28.0%, respectively, which indicated that there were significant differences in PFS and OS between the two groups (P<0.05). Additionally, RPA grading of each factor in the combination group was a risk factor closely related with survival, with medium PFS in EGFR and KRAS mutation patients being 8.2 months and 11.2 months, and OS being 3.6 months and 6.3 months, respectively. Conclusions: Whole brain radiotherapy concomitant with target therapy is favorable for adverse reaction tolerance and clinical effects, being superior in treating brain metastasis in NSCLC patients with chemotherapy failure and thus deserves to be widely applied in the clinic.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.8
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• pp.4679-4683
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• 2013

Background: ERCC1 is considered as a promising molecular marker that may predict platinum based chemotherapy response in non small cell lung cancer patients. We therefore investigated whether its expression is indeed associated with clinical outcomes in advanced stage NSCLC patients. Materials and Methods: Pretreatment tumor biopsy samples of 83 stage 3B and 4 non-small cell lung cancer patients treated with platinum based chemotherapy were retrospectively analyzed for immunohistochemical ERCC1 expression. None of the patients received curative surgery or radiotherapy. Results: By calculating H- scores regarding the extent and intensity of immunohistochemical staining of tumor biopsy samples, ERCC1 expression was found to be positive in 50 patients (60.2%). ERCC1 positive and negative groups had no statistically significant differences regarding treatment response, progression free survival and overall survival (respectively p=0.161; p=0.412; p=0.823). Conclusions: In our study we found no association between ERCC1 expression and survival or treatment response. The study has some limitations, such as small sample size and retrospective analysis method. There is need of more knowledge for use of ERCC1 guided chemotherapy regimens in advanced stage NSCLC.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.3
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• pp.933-939
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• 2015

Malignant tumors are often accompanied by increased risk of hematological abnormalities. However, few studies have reported any prognostic impact of preoperative thrombocytosis, leukocytosis and anemia in epithelia ovarian cancer (EOC). This study aimed to investigate preoperative hematological parameters for anemia, leukocytosis and thombocytosis in relation to established prognostic factors and survival in EOC cases. A total of 816 Chinese women treated for EOC were retrospectively included in the study focusing on the relationship between preoperative hemoglobin, leukocyte and platelet counts, and a panel of clinicopathologic characteristics and outcome. Preoperative anemia was present in 13.4%, leukocytosis in 16.7% and thrombocytosis in 22.8%. Additionally, EOC patients with low differentiation grade, advanced stage, lymph node (LN) metastasis, residual disease ${\geq}1cm$, ascites volume >1,000ml, serum cancer antigen 125 (CA125) >675U/ml, and disease recurrence had the higher prevalence of preoperative anemia, leukocytosis and thrombocytosis (all p<0.05). Moreover, EOC patients with older age or postmenopausal EOC patients had the higher prevalence of thrombocytosis (28.7% vs 17.3% or 26.0% vs 17.7%). Furthermore, in a Cox proportional hazard model, thrombocytosis was an independent factor for progression-free survival (PFS) and overall survival (OS) (p<0.001). Conclusively, preoperative anemia, leukocytosis or thrombocytosis in EOC patients is closely associated with more malignant disease phenotype and poorer prognosis. Significantly, thrombocytosis may independently predict the disease-specific survival for EOC patients.

• Journal of Korean Neurosurgical Society
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• v.45 no.5
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• pp.275-283
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• 2009

Objective : We retrospectively analyzed survival, local control rate, and incidence of radiation toxicities after radiosurgery for recurrent metastatic brain lesions whose initial metastases were treated with whole-brain radiotherapy. Various radiotherapeutical indices were examined to suggest predictors of radiation-related neurological dysfunction. Methods : In 46 patients, total 100 of recurrent metastases (mean 2.2, ranged 1-10) were treated by CyberKnife radiosurgery at average dose of 23.1 Gy in 1 to 3 fractions. The median prior radiation dose was 32.7 Gy, the median time since radiation was 5.0 months, and the mean tumor volume was $12.4cm^3$. Side effects were expressed in terms of radiation therapy oncology group (RTOG) neurotoxicity criteria. Results : Mass reduction was observed in 30 patients (65%) on MRI. After the salvage treatment, one-year progression-free survival rate was 57% and median survival was 10 months. Age(<60 years) and tumor volume affected survival rate(p=0.03, each). Acute (${\leq}$1 month) toxicity was observed in 22% of patients, subacute and chronic (>6 months) toxicity occurred in 21 %, respectively. Less acute toxicity was observed with small tumors (<$10cm^3$. p=0.03), and less chronic toxicity occurred at lower cumulative doses (<100 Gy, p=0.004). "Radiation toxicity factor" (cumulative dose times tumor volume of <1,000 Gy${\times}cm^3$) was a significant predictor of both acute and chronic CNS toxicities. Conclusion: Salvage CyberKnife radiosurgery is effective for recurrent brain metastases in previously irradiated patients, but careful evaluation is advised in patients with large tumors and high cumulative radiation doses to avoid toxicity.

• Radiation Oncology Journal
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• v.35 no.1
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• pp.55-64
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• 2017

Purpose: The outcomes and toxicities of locoregionally recurrent non-small-cell lung cancer (NSCLC) patients treated with curative radiotherapy were evaluated in the modern era. Materials and Methods: Fifty-seven patients receiving radical radiotherapy for locoregionally recurrent NSCLC without distant metastasis after surgery from 2004 to 2014 were reviewed. Forty-two patients were treated with concurrent chemoradiotherapy (CCRT), and 15 patients with radiotherapy alone. The median radiation dose was 66 Gy (range, 45 to 70 Gy). Lung function change after radiotherapy was evaluated by comparing pulmonary function tests before and at 1, 6, and 12 months after radiotherapy. Results: Median follow-up was 53.6 months (range, 12.0 to 107.5 months) among the survivors. The median overall survival (OS) and progression-free survival (PFS) were 54.8 months (range, 3.0 to 116.9 months) and 12.2 months (range, 0.8 to 100.2 months), respectively. Multivariate analyses revealed that single locoregional recurrence focus and use of concurrent chemotherapy were significant prognostic factors for OS (p = 0.048 and p = 0.001, respectively) and PFS (p = 0.002 and p = 0.026, respectively). There was no significant change in predicted forced expiratory volume in one second after radiotherapy. Although diffusing lung capacity for carbon monoxide decreased significantly at 1 month after radiotherapy (p < 0.001), it recovered to pretreatment levels within 12 months. Acute grade 3 radiation pneumonitis and esophagitis were observed in 3 and 2 patients, respectively. There was no chronic complication observed in all patients. Conclusion: Salvage radiotherapy showed good survival outcomes without severe complications in postoperative locoregionally recurrent NSCLC patients. A single locoregional recurrent focus and the use of CCRT chemotherapy were associated with improved survival. CCRT should be considered as a salvage treatment in patients with good prognostic factors.

• Radiation Oncology Journal
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• v.35 no.4
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• pp.332-339
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• 2017

Purpose: This study aimed to evaluate the prognostic effects of lymphovascular invasion (LVI) in triple-negative breast cancer (TNBC) patients who underwent surgical resection. Materials and Methods: A total of 63 non-metastatic TNBC patients who underwent surgical resection were retrospectively investigated from 2007 to 2016 in Inje University Busan Paik Hospital. Pathological tests revealed that 12 patients (19.0%) had LVI. Approximately 61.9% (n = 39) of the patients' samples stained positive for p53. Additional chemotherapy and radiotherapy (RT) were performed in 53 (84.1%) and 47 (74.6%) patients, respectively. Results: The median follow-up period was 39.5 months (range, 5.9 to 123.0 months). The pathological T stage (p = 0.008), N stage (p = 0.014), and p53 positivity (p = 0.044) were associated with LVI. Overall, the 3-year disease-free survival (DFS) rate and overall survival (OS) rate were 85.4% and 90.2%, respectively. Ten patients (15.9%) experienced relapse. LVI (n = 12) was associated with relapses (p = 0.016). p53 positivity was correlated with poor DFS (p = 0.048). Furthermore, LVI was related to poor DFS (p = 0.011) and OS (p = 0.001) and considered as an independent prognostic factor for DFS (p = 0.039). The 3-year DFS of patients with LVI (n = 12) was only 58.3%. Adjuvant RT minimized the negative prognostic effect of LVI on DFS (p = 0.068 [with RT] vs. p = 0.011 [without RT]). Conclusion: LVI was related to the detrimental effects of disease progression and survival of TNBC patients. Thus, a more effective treatment strategy is needed for TNBC patients with LVI.

• Journal of Breast Cancer
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• v.21 no.4
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• pp.399-405
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• 2018

Purpose: Vesicle-associated membrane protein 8 (VAMP8) is a soluble N-ethylmaleimide-sensitive factor receptor protein that participates in autophagy by directly regulating autophagosome membrane fusion and has been reported to be involved in tumor progression. Nevertheless, the expression and prognostic value of VAMP8 in breast cancer (BC) remain unknown. This study aimed to evaluate the clinical significance and biological function of VAMP8 in BC. Methods: A total of 112 BC samples and 30 normal mammary gland samples were collected. The expression of VAMP8 was assessed in both BC tissues and normal mammary gland tissues via a two-step immunohistochemical detection method. Results: The expression of VAMP8 in BC tissues was significantly higher than that in normal breast tissues. Furthermore, increased VAMP8 expression was significantly correlated with tumor size (p=0.007), lymph node metastasis (p=0.024) and recurrence (p=0.001). Patients with high VAMP8 expression had significantly lower cumulative recurrence-free survival and overall survival (p<0.001 for both) than patients with low VAMP8 expression. In multivariate logistic regression and Cox regression analyses, lymph node metastasis and VAMP8 expression were independent prognostic factors for BC. Conclusion: VAMP8 is significantly upregulated in human BC tissues and can thus be a practical and potentially effective surrogate marker for survival in BC patients.

• Tuberculosis and Respiratory Diseases
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• v.82 no.1
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• pp.62-70
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• 2019

Background: Epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancers have emerged as key predictive biomarkers in EGFR tyrosine kinase inhibitor (TKI) treatment. However, a few patients with wild-type EGFR also respond to EGFR TKIs. This study investigated the factors predicting successful EGFR TKI treatment in lung adenocarcinoma patients with wild-type EGFR. Methods: We examined 66 patients diagnosed with lung adenocarcinoma carrying wide-type EGFR who were treated with EGFR TKIs. The EGFR gene copy number was assessed by silver in situ hybridization (SISH). We evaluated the clinical factors and EGFR gene copy numbers that are associated with a favorable clinical response to EGFR TKIs. Results: The objective response rate was 12.1%, while the disease control rate was 40.9%. EGFR SISH analysis was feasible in 23 cases. Twelve patients tested EGFR SISH-positive, and 11 were EGFR SISH-negative, with no significant difference in tumor response and survival between EGFR SISH-positive and -negative patients. The overall median progression-free survival (PFS) and overall survival (OS) of 66 patients were 2.1 months and 9.7 months, respectively. Female sex and Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1 were independent predictors of PFS. ECOG PS 0-1 and a low tumor burden of extrathoracic metastasis were independent predictors of good OS. Conclusion: Factors such as good PS, female sex, and low tumor burden may predict favorable outcomes following EGFR TKI therapy in patients with EGFR wild-type lung adenocarcinoma. However, EGFR gene copy number was not predictive of survival.

• Journal of Gastric Cancer
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• v.21 no.2
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• pp.155-168
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• 2021

Purpose: Previous studies have demonstrated the usefulness of the controlling nutritional status (CONUT) score in nutritional assessment and survival prediction of patients with various malignancies. However, its value in advanced gastric cancer (GC) treated with neoadjuvant chemotherapy and curative gastrectomy remains unclear. Materials and Methods: The CONUT score at different time points (pretreatment, preoperative, and postoperative) of 272 patients with advanced GC were retrospectively calculated from August 2004 to October 2015. The χ² test or Mann-Whitney U test was used to estimate the relationships between the CONUT score and clinical characteristics as well as short-term outcomes, while the Cox proportional hazard model was used to estimate long-term outcomes. Survival curves were estimated by using the Kaplan-Meier method and log-rank test. Results: The proportion of moderate or severe malnutrition among all patients was not significantly changed from pretreatment (13.5%) to pre-operation (11.7%) but increased dramatically postoperatively (47.5%). The pretreatment CONUT-high score (≥4) was significantly associated with older age (P=0.010), deeper tumor invasion (P=0.025), and lower pathological complete response rate (CONUT-high vs. CONUT-low: 1.2% vs. 6.6%, P=0.107). Pretreatment CONUT-high score patients had worse progression-free survival (P=0.032) and overall survival (OS) (P=0.026). Adjusted for pathologic node status, the pretreatment CONUT-high score was strongly associated with worse OS in pathologic node-positive patients (P=0.039). Conclusions: The pretreatment CONUT score might be a straightforward index for immune-nutritional status assessment, while being a reliable prognostic indicator in patients with advanced GC receiving neoadjuvant chemotherapy and curative gastrectomy. Moreover, lower pretreatment CONUT scores might indicate better chemotherapy responses.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.3
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• pp.785-789
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• 2012

Background and Purpose: Cisplatin is the most common chemotherapeutic agent for loco-regionally advanced nasopharyngeal carcinoma (NPC); however, toxicity is a limiting factor for some patients. We retrospectively compared the efficacy and toxicity of weekly docetaxel-based and cisplatin-based concurrent chemoradiotherapy in loco-regionally advanced NPC. Methods and Materials: Eighty-four patients with Stage III and IVA-B NPCs, treated between 2007 and 2008, were retrospectively analyzed. Thirty received weekly docetaxel-based concurrent chemotherapy, and 43 were given weekly cisplatin-based concurrent chemotherapy. Radiotherapy was administered using a conventional technique (seven weeks, 2.0 Gy per fraction, total dose 70-74 Gy) with 6-8 Gy boosts for some patients with locally advanced disease. Results: Median follow-up time was 42.3 months (range, 8.6-50.8 months). There were no significant differences in the 3-year loco-regional failure-free survival (85.6% vs. 92.3%; p=0.264), distant failure-free survival (87.0% vs. 92.5%; p=0.171), progression-free survival (85.7% vs. 88.4%; p=0.411) or overall survival (86.5% vs. 92.5%, p=0.298) of patients treated concurrently with docetaxel or cisplatin. Severe toxicity was not common in either group. Conclusions: Weekly docetaxel-based concurrent chemoradiotherapy is potentially effective and has a tolerable toxicity; however, further investigations are required to determine if docetaxel is superior to cisplatin for advanced stage NPC.