• Journal of Gastric Cancer
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• 제21권1호
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• pp.49-62
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• 2021

Purpose: This study aimed to investigate the prognostic value of lymph node ratio (LNR) in patients with locally advanced gastric cancer who received neoadjuvant chemotherapy. Materials and Methods: We retrospectively enrolled gastric cancer patients treated with neoadjuvant chemotherapy and curative surgery at the First Affiliated Hospital of Zhejiang University from 2004 to 2015 as the study cohort. Patients with the same inclusion criteria treated in 2016-2017 were enrolled as the validation cohort. Kaplan-Meier curves were assessed using the log-rank test to analyze the differences in overall survival (OS). Multivariate survival analysis was performed using the Cox proportional hazards model. The areas under the receiver operating characteristic curve of ypN and LNR categories for predicting the actual 3-year OS were compared. Results: A total of 265 patients were included in the proposal cohort. The median number of retrieved lymph nodes (rLNs) was 32. The number of positive lymph nodes (pLNs) increased as rLN increased (P=0.037), but the LNR remained relatively constant (P=0.462). The LNR was categorized into 4 groups according to the prognosis: ypNr0, node-negative with rLN>25; ypNr1, node-negative with rLN≤25 or 00.3. In the validation cohort of 43 enrolled patients, there was a clear distinction in OS that significantly (P<0.001) varied depending on the LNR values and LNR was the only independent prognostic factor in multivariate analysis (P<0.001). Conclusions: LNR was an independent prognostic factor for survival of patients with gastric cancer after preoperative chemotherapy and might be an alternative predictor for ypN stage.

• Journal of Gastric Cancer
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• 제17권1호
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• pp.74-87
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• 2017

Purpose: Neoadjuvant chemotherapy has been shown to improve survival in locally advanced gastric cancer, but it is associated with significant toxicity. Sarcopenia and sarcopenic obesity have been studied in several types of cancers and have been reported to be associated with higher chemotherapy toxicity and morbi-mortality. The aim of this study was to assess the prevalence of sarcopenia/sarcopenic obesity in patients with gastric cancer, as well as its association with chemotherapy toxicity and long-term outcomes. Materials and Methods: A retrospective analysis was performed using an academic cancer center patient cohort diagnosed with locally advanced gastric cancer between January 2012 and December 2014 and treated with neoadjuvant chemotherapy. We analyzed body composition (skeletal muscle and visceral fat index) in axial computed tomography images. Results: A total of 48 patients met the inclusion criteria. The mean age was $68{\pm}10years$, and 33 patients (69%) were men. Dose-limiting toxicity was observed in 22 patients (46%), and treatment was terminated early owing to toxicity in 17 patients (35%). Median follow-up was 17 months. Sarcopenia and sarcopenic obesity were found at diagnosis in 23% and 10% of patients, respectively. We observed an association between termination of chemotherapy and both sarcopenia (P=0.069) and sarcopenic obesity (P=0.004). On multivariate analysis, the odds of treatment termination were higher in patients with sarcopenia (odds ratio=4.23; P=0.050). Patients with sarcopenic obesity showed lower overall survival (median survival of 6 months [95% confidence interval {CI}=3.9-8.5] vs. 25 months [95% CI=20.2-38.2]; log-rank test P=0.000). Conclusions: Sarcopenia and sarcopenic obesity were associated with early termination of neoadjuvant chemotherapy in patients with gastric cancer; additionally, sarcopenic obesity was associated with poor survival.

• Journal of Gastric Cancer
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• 제23권2호
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• pp.328-339
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• 2023

Purpose: This study aimed to evaluate the efficacy and safety of neoadjuvant programmed cell death-1 (PD-1) inhibitors plus apatinib and chemotherapy (PAC) in patients with locally advanced gastric cancer (LAGC). Materials and Methods: Seventy-three patients with resectable LAGC were enrolled and named the PAC group (n=39) or apatinib plus chemotherapy (AC) group (n=34) based on the treatment they chose. Neoadjuvant therapy was administered in a 21-day cycle for 3 consecutive cycles, after which surgery was performed. Results: The PAC group exhibited a higher objective response rate than the AC group (74.4% vs. 58.8%, P=0.159). Moreover, the PAC group showed a numerically better response profile than the AC group (P=0.081). Strikingly, progression-free survival (PFS) (P=0.019) and overall survival (OS) (P=0.049) were prolonged, whereas disease-free survival (DFS) tended to be longer in the PAC group than in the AC group (P=0.056). Briefly, the 3-year PFS, DFS, and OS rates were 76.1%, 76.1%, and 86.7% in the PAC group and 46.9%, 49.9%, and 70.3% in the AC group, respectively. Furthermore, PAC (vs. AC) treatment (hazard ratio=0.286, P=0.034) was independently associated with prolonged PFS in multivariate Cox regression analyses. The incidence of adverse events did not differ between the two groups (all P>0.05), where leukopenia, anemia, hypertension, and other adverse events were commonly observed in the PAC group. Conclusions: Neoadjuvant PAC therapy may achieve a preferable pathological response, delayed progression, and prolonged survival compared to AC therapy with a similar safety profile in patients with LAGC; however, further validation is warranted.

• Asian Pacific Journal of Cancer Prevention
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• 제16권11호
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• pp.4603-4608
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• 2015

Background: To determine the potential value of serum tumor markers in predicting pCR (pathological complete response) during neoadjuvant chemotherapy. Materials and Methods: We retrospectively monitored the pro-, mid-, and post-neoadjuvant treatment serum tumor marker concentrations in patients with locally advanced breast cancer (stage II-III) who accepted pre-surgical chemotherapy or chemotherapy in combination with targeted therapy at Fudan University Shanghai Cancer Center between September 2011 and January 2014 and investigated the association of serum tumor marker levels with therapeutic effect. Core needle biopsy samples were assessed using immunohistochemistry (IHC) prior to neoadjuvant treatment to determine hormone receptor, human epidermal growth factor receptor 2(HER2), and proliferation index Ki67 values. In our study, therapeutic response was evaluated by pCR, defined as the disappearance of all invasive cancer cells from excised tissue (including primary lesion and axillary lymph nodes) after completion of chemotherapy. Analysis of variance of repeated measures and receiver operating characteristic (ROC) curves were employed for statistical analysis of the data. Results: A total of 348 patients were recruited in our study after excluding patients with incomplete clinical information. Of these, 106 patients were observed to have acquired pCR status after treatment completion, accounting for approximately 30.5% of study individuals. In addition, 147patients were determined to be Her-2 positive, among whom the pCR rate was 45.6% (69 patients). General linear model analysis (repeated measures analysis of variance) showed that the concentration of cancer antigen (CA) 15-3 increased after neoadjuvant chemotherapy in both pCR and non-pCR groups, and that there were significant differences between the two groups (P=0.008). The areas under the ROC curves (AUCs) of pre-, mid-, and post-treatment CA15-3 concentrations demonstrated low-level predictive value (AUC=0.594, 0.644, 0.621, respectively). No significant differences in carcinoembryonic antigen (CEA) or CA12-5 serum levels were observed between the pCR and non-pCR groups (P=0.196 and 0.693, respectively). No efficient AUC of CEA or CA12-5 concentrations were observed to predict patient response toward neoadjuvant treatment (both less than 0.7), nor were differences between the two groups observed at different time points. We then analyzed the Her-2 positive subset of our cohort. Significant differences in CEA concentrations were identified between the pCR and non-pCR groups (P=0.039), but not in CA15-3 or CA12-5 levels (p=0.092 and 0.89, respectively). None of the ROC curves showed underlying prognostic value, as the AUCs of these three markers were less than 0.7. The ROC-AUCs for the CA12-5 concentrations of inter-and post-neoadjuvant chemotherapy in the estrogen receptor negative HER2 positive subgroup were 0.735 and 0.767, respectively. However, the specificity and sensitivity values were at odds with each other which meant that improving either the sensitivity or specificity would impair the efficiency of the other. Conclusions: Serum tumor markers CA15-3, CA12-5, and CEA might have little clinical significance in predicting neoadjuvant treatment response in locally advanced breast cancer.

• Clinical and Experimental Pediatrics
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• 제45권12호
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• pp.1534-1539
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• 2002

목 적 : Wilms 종양은 진행된 경우에서도 수술, 방사선 치료, 항암화학요법의 병합요법으로 치료 성적이 우수하지만 방사선 치료로 인한 후기 합병증이 문제가 될 수 있다. 본 연구에서는 진행된 Wilms 종양(병기 3기, 4기)에서 수술 전 화학요법을 시행하여 종양의 완전 절제율을 높임으로써 방사선 치료를 생략하고자 하였다. 방 법 : 저자들은 1998년 12월부터 2002년 7월까지 삼성서울병원에서 Wilms 종양으로 치료를 시작한 환자 중 침 생검 후 수술 전 화학요법을 시행하였던 환자를 대상으로 하였다. 진단 시 3기, 4기의 환자에서 침 생검이 가능한 경우 수술 전 항암화학요법(vincristine, adriamycin, dactinomycin)을 12주간 시행 후 종양의 크기가 감소하면 종양 절제술을 시행하였고 완전 절제가 된 경우 방사선 치료를 생략하고 수술 후 화학요법(vincristine, dactinomycin${\pm}$adriamycin)을 시행하였다. 침 생검이 기술적으로 어렵거나 위험하다고 생각되었던 경우에는 먼저 수술적으로 종양을 절제하고 방사선 치료와 화학요법을 시행하였다. 결 과 : 연구기간 중 삼성서울병원에서 치료를 시작한 17례의 Wilms 종양 중 3기, 4기는 12례였고 이중 2례에서는 침생검이 불가능하여 먼저 수술적으로 종양을 절제하였고 침생검이 가능하였던 경우는 10례였다. 이들의 진단 시 정중 연령은 21개월(5개월-103개월)이었고, 진단 후 정중 추적기간은 31개월(9개월-44개월)이었다. 수술 전 화학요법을 시행한 10례 중 2례를 제외한 8례에서 수술시 병기가 1기로 하향화되었으며, 수술시 병기가 2기였던 1례와 함께 총 9례에서 종양의 완전절제가 가능했고 방사선 치료도 생략할 수 있었다. 이들 중 4례에서는 adriamycin도 치료에서 제외하였다. 종양의 완전 절제에 실패한 1례는 결국 사망하였고, 1례는 재발하였으나 강화된 항암화학요법과 수술로 다시 관해에 도달하여 현재 10례 중 9례가 무병 생존 중이다. 결 론 : 진행된 Wilms 종양에서 수술 전 화학요법을 시행하여 종양의 완전 절제율을 높이고 방사선 치료를 생략할 수 있었으며, 일부 환자에서는 수술 후 화학요법의 강도를 감소시킬 수 있었다. 향후 생존율의 저하 없이 후기 합병증을 줄일 수 있을 지에 대한 연구가 필요할 것으로 사료된다.

• Asian Pacific Journal of Cancer Prevention
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• 제17권2호
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• pp.807-813
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• 2016

Triple-negative breast cancers constitute about 15% of all cases, but despite their higher response to neoadjuvant chemotherapy, the tumors are very aggressive and associated with a poor prognosis as well as a higher risk of early recurrence. This study was retrospectively performed on 101 patients with stage II and III invasive breast cancer who received 6-8 cycles of neo-adjuvant chemotherapy. Out of the total, 23 were in the triple negative breast cancer subgroup. Nuclear Ki-67 expression in both the large cohort group (n=101) and triple negative breast cancer subgroup (n=23) and its relation to the pathological response were evaluated. The purpose of the study was to identify the predictive value of nuclear protein Ki-67 expression among patients with invasive breast cancers, involving the triple negative breast cancer subgroup, treated with neoadjuvant chemotherapy in correlation to the rate of pathological complete response. The proliferation marker Ki-67 expression was highest in the triple negative breast cancer subgroup. No appreciable difference in the rate of Ki-67 expression in triple negative breast cancer subgroup using either a cutoff of 14% or 35%. Triple negative breast cancer subgroup showed lower rates of pathological complete response. Achievement of pathological complete response was significantly correlated with smaller tumor size and higher Ki-67 expression. The majority of triple negative breast cancer cases achieved pathological partial response. The study concluded that Ki-67 is a useful tool to predict chemosensitivity in the setting of neoadjuvant chemotherapy for invasive breast cancer but not for the triple negative breast cancer subgroup.

• Journal of Breast Cancer
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• 제21권4호
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• pp.425-432
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• 2018

Purpose: Pregnancy-associated breast cancer (PABC) is rare, and its cause and prognosis are not well known. Additionally, treatment is limited with respect to the risk to the fetus. The purpose of this study was to investigate the characteristics and treatment trends of PABC and the survival rate according to the treatment. Methods: In the Korean Breast Cancer Society Registry database, women younger than 50 years and who were diagnosed with breast cancer from 1996 to 2015 were included. PABC was defined as breast cancer diagnosed during pregnancy or within 1 year after delivery. Results: We examined 411 patients with PABC and 83,381 patients with non-PABC. Over time, the proportions of patients undergoing breast-conserving surgery and sentinel lymph node biopsy increased, and neoadjuvant chemotherapy and radiation therapy administration rates also increased. In the past, the overall survival of patients with PABC was poorer than that of patients with non-PABC, but there was no difference in overall survival rates in more recent years. There was no difference in overall survival rates between patients who received neoadjuvant chemotherapy (hazard ratio [HR], 1.28; 95% confidence interval [CI], 0.66-2.49; p=0.459), but PABC conferred poorer prognosis than non-PABC in patients receiving adjuvant chemotherapy (HR, 1.63; 95% CI, 1.27-2.08; p<0.001). Conclusion: There was no difference in the prognosis between patients with PABC and those with non-PABC receiving neoadjuvant chemotherapy. The increase in neoadjuvant chemotherapy according to current treatment guidelines is expected to improve the survival rate of patients with PABC.

• 대한골관절종양학회지
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• 제20권2호
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• pp.66-73
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• 2014

목적: 골육종에 대한 술전 항암화학요법의 효과를 조기에 비침습적으로 평가하기 위해 다양한 영상 진단 기법들을 사용해 왔다. 저자들은 골육종에 대한 술전 항암화학요법의 효과를 예측하는 데 있어 단순 촬영 및 양전자 방출 단층 촬영과 같은 영상 검사들의 효용성을 평가하고 양성자 방출 단층 촬영에서 얻어진 값들을 해석하는 데 있어서의 통칙을 정해 보고자 하였다. 대상 및 방법: 2주기 술전 항암화학요법 후 외과적 절제를 시행한 18명의 골육종 환자들을 대상으로 하였다. 남자 13명, 여자 5명이었으며, 연령의 중위수는 19세였다. 술전 항암화학요법의 전후로 단순 촬영 및 양전자 방출 단층 촬영을 시행하였다. 절제된 종양에 대해 병리검사를 시행하여 조직학적 반응 등급을 확인하였다. 조직병리학적 괴사 정도와 방사선학적 소견, 술전 항암화학요법 후 최대 표준섭취계수(maximum standardized uptake value), 평균 표준섭취계수(average standardized uptake value), 대사종양용적(metabolic tumor volume) 및 해당 값들의 감소율에 대해 통계학적 분석을 시행하였다. 결과: 조직학적 평가 상, 8명의 환자에서 술전 항암화학요법에 대해 좋은 반응을 확인하였다. 최대 표준섭취계수 감소율의 중위수는 좋은 반응을 보인 군에서 74 (23-77) %였고, 나머지에서 42 (-32-76) %였다. 대사종양용적 감소율의 중위수는 좋은 반응을 보인 군에서 93.5 (62-99) %였고 나머지에서 46 (-81-100) %였다. 방사선학적 소견의 범주는 조직학적 반응에 따른 차이가 없었지만 (p=1.0), 최대 표준섭취계수의 감소율은 유의한 차이를 보였다(p=0.041). 대사종양용적의 감소율 차이는 통계학적 유의성에 근접하였다(p=0.071). 결론: 본 연구에서 방사선학적 소견의 범주는 골육종에 대한 술전 항암화학요법의 효과를 평가하는 데 있어 신뢰할 수 없었지만, 최대 표준섭취계수는 유용한 척도였다. 양전자 방출 단층 촬영에서 얻어지는 값들은 여러 요인에 의해 영향을 받으므로, 각 기관은 기왕의 연구들을 참고로 각자의 판단 기준을 마련하기 위해 노력해야만 한다.

• Asian Pacific Journal of Cancer Prevention
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• 제17권12호
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• pp.5315-5320
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• 2016

Purpose: Tumor cell growth and sensitivity to chemotherapy depend on many factors, among which insulin-like growth factors (IGFs) may play important roles. The aim of the present study was to evaluate the levels of insulin-like growth factors (IGFs) and IGF binding proteins (IGFBPs) in primary tumors and ascites as predictors of response to neoadjuvant chemotherapy in ovarian cancer (OC) patients. Materials and Methods: Tumor tissue samples and ascitic fluid were obtained from 59 patients with advanced OC. The levels of IGF-I, IGF-II, IGFBP-3, IGFBP-4 and PAPP-A were determined using ELISA kits. Taking into account the data on expression of these IGF-related proteins and outcome, logistic regression was performed to identify predictors of response to neoajuvant chemotherapy. Results: Human ovarian tumors expressed IGFs, IGFBP-3, IGFBP-4 and PAPP-A and these proteins were also present in ascites fluid and associated with its volume. IGFs and IGFBPs in ascites and soluble PAPP-A might play a key role in ovarian cancer progression. However, levels of proteins of the IGF system in tumors were not significant predictors of objective clinical response (oCR). Univariate analysis showed that the level of IGF-I in ascites was the only independent predictor for oCR. Conclusion: The level of IGF-I in ascites was shown to be an independent predictor of objective clinical response to chemotherapy for OC patients treated with neoadjuvant chemotherapy and debulking surgery.

• 한국간담췌외과학회지
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• 제27권1호
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• pp.114-119
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• 2023

A 51-year-old male patient had four times of massive hematochezia episode three days before arrival. Carbohydrate antigen (CA) 19-9 level was extremely elevated. Computed tomography, magnetic resonance imaging, and positron emission tomography-computed tomography identified 5.7 cm sized periampullary duodenal cancer with regional metastatic lymph nodes and vascular invasion to aberrant right hepatic artery, main portal vein, and superior mesenteric vein. Diagnosed as duodenal adenocarcinoma through endoscopic biopsy, 16 times of FOLFIRI (5-fluorouracil, leucovorin, irinotecan) was conducted. The regimen changed to XELOX (capecitabine, oxaliplatine), four times of administration was done, and the CA19-9 level dramatically decreased. The tumor decreased to 2.1 cm. After R0 laparoscopic pylorus preserving pancreatoduodenectomy, no adjuvant therapy was given. No sign of recurrence or metastasis was reported, and the patient reached complete remission after five years. We reported a case where neoadjuvant chemotherapy for locally advanced duodenal adenocarcinoma was shown to be effective.