• Radiation Oncology Journal
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• v.36 no.3
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• pp.218-226
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• 2018

Purpose: Standard treatment for locally advanced rectal cancer consists of neoadjuvant radiochemotherapy with concomitant fluoropyrimidine or oxaliplatin and surgery with curative intent. Pathological complete response has shown to be predictive for better outcome and survival; nevertheless there are no biological or genetic factors predictive for response to treatment. We explored the correlation between the single nucleotide polymorphisms (SNPs) GSTP1 (A313G) and XRCC1 (G28152A), and the pathological complete response and survival after neoadjuvant radiochemotherapy in locally advanced rectal cancer patients. Materials and Methods: Genotypes GSTP1 (A313G) and XRCC1 (G28152A) were determined by pyrosequencing technology in 80 patients affected by locally advanced rectal cancer. Results: The overall rate of pathological complete response in our study population was 18.75%. Patients homozygous AA for GSTP1 (A313G) presented a rate of pathological complete response of 26.6% as compared to 8.5% of the AG+GG population (p = 0.04). The heterozygous comparison (AA vs. AG) showed a significant difference in the rate of pathological complete response (26.6% vs. 6.8%; p = 0.034). GSTP1 AA+AG patients presented a 5- and 8-year cancer-specific survival longer than GSTP1 GG patients (87.7% and 83.3% vs. 44.4% and 44.4%, respectively) (p = 0.014). Overall survival showed only a trend toward significance in favor of the haplotypes GSTP1 AA+AG. No significant correlations were found for XRCC1 (G28152A). Conclusion: Our results suggest that GSTP1 (A313G) may predict a higher rate of pathological complete response after neoadjuvant radiochemotherapy and a better outcome, and should be considered in a more extensive analysis with the aim of personalization of radiation treatment.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.4
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• pp.1775-1781
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• 2014

Background: To assess the long term clinical outcome of preoperative radiotherapy with or without chemotherapy followed by limb sparing surgery in patients with non-metastatic soft tissue sarcomas (STS) of the extremities. Materials and Methods: Sixty patients with locally advanced STS were retrospectively analyzed. The median tumor diameter was 12 cm. All patients were treated with preoperative radiotherapy delivered with two different fractionation schedules (35Gy/10fr or 46-50Gy/23-25fr). Neoadjuvant chemotherapy was added to 44 patients with large and/or high grade tumors. Surgery was performed 2-6 weeks after radiotherapy. Chemotherapy was completed up to 6 courses after surgery in patients who had good responses. Results: Median follow-up time was 67 months (8-268 months). All of the patients had limb sparing surgery. The 5-year local control (LC), disease free (DFS) and overall survival (OSS) rates for all of the patients were 81%, 48.1% and 68.3% respectively. 5-year LC, DFS and cause specific survival (CSS) were 81.7%, 47%, 69.8%, and 80%, 60%, 60% in the chemoradiotherapy and radiotherapy groups, respectively. On univariate analysis, patients who were treated with hypofractionation experienced significantly superior LC, DFS and CSS rates with similar rates of late toxicity when compared with patients who were treated with conventional fractionation and statistical significance was retained on multivariate analysis. Conclusions: Treatment results are consistent with the literature. As neoadjuvant chemoradiotherapy provides effective LC and CSS with acceptable morbidity, it should be preferred for patients with large and borderline resectable STS.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6419-6425
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• 2013

Background: Neoadjuvant chemotherapy (NACT) is a treatment modality whereby chemotherapy is used as the initial treatment of HNSCC in patients presenting with advanced cancer that cannot be treated by other means. It leads to shrinkage of tumours to an operable size without significant compromise to essential oro-facial organs of the patients. The molecular mechanisms behind shrinkage due to NACT is not well elucidated. Materials and Methods: Eleven pairs of primary HNSCCs and adjacent normal epithelium, before and after chemotherapy were screened for cell proliferation and apoptosis. This was followed by immunohistochemical analysis of some cell cycle (LIMD1, RBSP3, CDC25A, CCND1, cMYC, RB, pRB), DNA repair (MLH1, p53) and apoptosis (BAX, BCL2) associated proteins in the same set of samples. Results: Significant decrease in proliferation index and increase in apoptotic index was observed in post-therapy tumors compared to pre-therapy. Increase in the RB/pRB ratio, along with higher expression of RBSP3 and LIMD1 and lower expression of cMYC were observed in post-therapy tumours, while CCND1 and CDC25A remained unchanged. While MLH1 remained unchanged, p53 showed higher expression in post-therapy tumors, indicating inhibition of cell proliferation and induction of apoptosis. Increase in the BAX/BCL2 ratio was observed in post-therapy tumours, indicating up-regulation of apoptosis in response to therapy. Conclusions: Thus, modulation of the G1/S cell cycle regulatory proteins and apoptosis associated proteins might play an important role in tumour shrinkage due to NACT.

• Journal of Gastric Cancer
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• v.20 no.4
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• pp.385-394
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• 2020

Purpose: Patients with gastric cancer who receive neoadjuvant therapy are staged before treatment (cStage) and after treatment (ypStage). We aimed to compare the prognostic reliability of cStage and ypStage, alone and in combination. Materials and Methods: Data for all patients who received neoadjuvant therapy followed by surgery for gastric adenocarcinoma from 2004 to 2015 were extracted from the National Cancer Database. Kaplan-Meier (KM)curves were used to model overall survival based on cStage alone, ypStage alone, cStage stratified by ypStage, and ypStage stratified by cStage. P-values were generated to summarize the differences in KM curves. The discriminatory power of survival prediction was examined using Harrell's C-statistics. Results: We included 8,977 patients in the analysis. As expected, increasing cStage and ypStage were associated with worse survival. The discriminatory prognostic power provided by cStage was poor (C-statistic 0.548), while that provided by ypStage was moderate (C-statistic 0.634). Within each cStage, the addition of ypStage information significantly altered the prognosis (P<0.0001 within cStages I-IV). However, for each ypStage, the addition of cStage information generally did not alter the prognosis (P=0.2874, 0.027, 0.061, 0.049, and 0.007 within ypStages 0-IV, respectively). The discriminatory prognostic power provided by the combination of cStage and ypStage was similar to that of ypStage alone (C-statistic 0.636 vs. 0.634). Conclusions: The cStage is unreliable for prognosis, and ypStage is moderately reliable. Combining cStage and ypStage does not improve the discriminatory prognostic power provided by ypStage alone. A ypStage-based prognosis is minimally affected by the initial cStage.

• Korean Journal of Radiology
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• v.20 no.5
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• pp.801-811
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• 2019

Objective: To determine whether diffusion kurtosis imaging (DKI) is effective in monitoring tumor response to neoadjuvant chemotherapy in patients with osteosarcoma. Materials and Methods: Twenty-nine osteosarcoma patients (20 men and 9 women; mean age, 17.6 ± 7.8 years) who had undergone magnetic resonance imaging (MRI) and DKI before and after neoadjuvant chemotherapy were included. Tumor volume, apparent diffusion coefficient (ADC), mean diffusivity (MD), mean kurtosis (MK), and change ratio (ΔX) between pre-and post-treatment were calculated. Based on histologic response, the patients were divided into those with good response (≥ 90% necrosis, n = 12) and those with poor response (< 90% necrosis, n = 17). Several MRI parameters between the groups were compared using Student's t test. The correlation between image indexes and tumor necrosis was determined using Pearson's correlation, and diagnostic performance was compared using receiver operating characteristic curves. Results: In good responders, MD_post, ADC_post, and MK_post values were significantly higher than in poor responders (p < 0.001, p < 0.001, and p = 0.042, respectively). The ΔMD and ΔADC were also significantly higher in good responders than in poor responders (p < 0.001 and p = 0.01, respectively). However, no significant difference was observed in ΔMK (p = 0.092). MD_post and ΔMD showed high correlations with tumor necrosis rate (r = 0.669 and r = 0.622, respectively), and MD_post had higher diagnostic performance than ADC_post (p = 0.037) and MK_post (p = 0.011). Similarly, ΔMD also showed higher diagnostic performance than ΔADC (p = 0.033) and ΔMK (p = 0.037). Conclusion: MD is a promising biomarker for monitoring tumor response to preoperative chemotherapy in patients with osteosarcoma.

• Journal of Gastric Cancer
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• v.23 no.3
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• pp.499-508
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• 2023

Purpose: Despite scientific evidence regarding laparoscopic gastrectomy (LG) for advanced gastric cancer treatment, its application in patients receiving neoadjuvant chemotherapy remains uncertain. Materials and Methods: We used the 2019 Korean Gastric Cancer Association nationwide survey database to extract data from 489 patients with primary gastric cancer who received neoadjuvant chemotherapy. After propensity score matching analysis, we compared the surgical outcomes of 97 patients who underwent LG and 97 patients who underwent open gastrectomy (OG). We investigated the risk factors for postoperative complications using multivariate analysis. Results: The operative time was significantly shorter in the OG group. Patients in the LG group had significantly less blood loss than those in the OG group. Hospital stay and overall postoperative complications were similar between the two groups. The incidence of Clavien-Dindo grade ≥3 complications in the LG group was comparable with that in the OG group (1.03% vs. 4.12%, P=0.215). No statistically significant difference was observed in the number of harvested lymph nodes between the two groups (38.60 vs. 35.79, P=0.182). Multivariate analysis identified body mass index (odds ratio [OR], 1.824; 95% confidence interval [CI], 1.029-3.234; P=0.040) and extent of resection (OR, 3.154; 95% CI, 1.084-9.174; P=0.035) as independent risk factors for overall postoperative complications. Conclusions: Using a large nationwide multicenter survey database, we demonstrated that LG and OG had comparable short-term outcomes in patients with gastric cancer who received neoadjuvant chemotherapy.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.2
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• pp.771-774
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• 2016

Thymic tumors are the most common tumors in the anterior mediastinum. Total resection is the main treatment and predictor of longer survival. Adjuvant radiotherapy alone or in combination with chemotherapy is recommended with incomplete excision or advanced disease. Thirty seven patients with thymic tumors were included in this retrospective study from January 2001 till December 2012. They were studied regarding age, sex, performance status, tumor size and invasion, stage, pathology, treatment given, overall and progression free survival. Myasthenia gravis was present in 18.1% of the patients. Masaoka stage III was diagnosed in 40.5% of the cases followed by stage II in 24.3% and the other stages with lower percentages. Pathology type B3 was the most frequent followed by B2 and B1 with percentages of 27, 24.3 and 21.7 respectively. Complete resection was conducted in 11 cases (29.75%). Partial resection or debulking was done in 15 (40.5%) and a biopsy was taken in 11 cases (29.8%) Adjuvant chemotherapy was given to 14 patients (37.8%) and neoadjuvant to 13 (35.2%). Adjuvant radiotherapy was given to 17 patients (46%) and neoadjuvant to 14 (37.8%). The 5-year overall survival by was 83% for stage I, 71% for stage II, 60% for stage III, and 44% for stage IV (p=0.0426). Five year progression free survival was 71% for stage I, 62% stage II, 42% stage III, and 37% for stage IV (p=0.0532). In conclusion with the rare thymic tumors early stage and complete resection have the highest impact on overall and progression free survival.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.2
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• pp.713-718
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• 2015

Background: A number of association studies have been carried out to investigate the relationship between genetic polymorphisms in DNA repair genes and response to radiotherapy-based multimodality treatment of patients with rectal cancer. However, their conclusions were inconsistent. The objective of the present study was to assess the role of DNA repair gene genetic polymorphisms in predicting genetic biomarkers of the response in rectal cancer patients treated with neoadjuvant chemoradiation. Materials and Methods: Studies were retrieved by searching the PubMed database, Cochrane Library, Embase, and ISI Web of Knowledge. We conducted a meta-analysis to evaluate the association between genetic polymorphisms and the response in rectal cancer treated with neoadjuvant chemoradiation by checking odds ratios (ORs) and 95% confidence intervals (CIs). Results: Data were extracted from 5 clinical studies for this meta-analysis. The results showed that XRCC1 RS25487, XRCC1 RS179978, XRCC3 RS861539, ERCC1 RS11615 and ERCC2 RS13181 were not associated with the response in the radiotherapy-based multimodality treatment of patients with rectal cancer (p>0.05). Conclusions: This study shows that DNA repair gene common genetic polymorphisms are not significantly correlated with the radiotherapy-based multimodality treatment in rectal cancer patients.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.21
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• pp.9379-9383
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• 2014

Background: Pathologic complete response (pCR) is one of the most important target end-points of neoadjuvant chemotherapy (NACT) in patients with breast cancer (BC). In present study, we aimed to investigate the relationship between molecular subtypes and NACT in patients with BC. Materials and Methods: Using the Akdeniz University database, 106 patients who received NACT for operable breast cancer were retrospectively identified. Prognostic factors before and after NACT were assessed. According to the molecular subtypes, molecular shifting after NACT and tumoral and nodal response to NACT were analyzed. Results: The distribution of subtypes was: Luminal A, 28.3% (n=30); Luminal B, 31.1% (n=33); HER2-like, 24.5% (n=26); and basal like/triple negative (BL/TN), 16.0% (n=17). According to molecular subtypes, pCR rates in both breast and axillary were 0%, 21.4%, 36.4% and 27.3% for luminal A, luminal B, HER2-like and BL/TN, respectively (p=0.018). Molecular subtype shifting was mostly seen in luminal A type (28.6%) after the NACT. The pCR rate in breast and axillary was significantly higher in patients with HER2-like type BC. Conclusions: In patients with HER-2 like type BC, NACT may be offered in early stages. Additionally, due to molecular shifting, adjuvant treatment schedule should be reviewed again, especially in the luminal A group.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.18
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• pp.7737-7740
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• 2014

Background: The neutrophil-to-lymphocyte ratio (NLR) is a strong predictor of mortality in patients with pancreatic, colorectal, lung, gastric cancer and renal cell carcinoma. The aim of this study was to determine the relationship between pathological complete response (pCR) and pretreatment NLR values in locally advanced breast cancer (BC) patients receiving neoadjuvant chemotherapy (NACT). Materials and Methods: Datawere collected retrospectively from the Akdeniz University School of Medicine Database for locally advanced BC patients treated with NACT between January 2000-December 2013. Results: A total of 78 patients were analyzed. Sixteen (20%) patients achieved pCR. Estrogen receptor (ER) positivity was lower in pCR+ than pCR-cases (p=0.011). The median NLR values were similar in both arms. The optimum NLR cut-off point for BC patients with PCR+ was 2.33 (AUC:0.544, 95%CI [0.401-0.688], p=0.586) with sensitivity, specificity, positive predictive value and negative predictive value (NPV) of 50%, 51,6%, 21,1%, and 80%, respectively. Conclusions: This study showed no relationship between the pCR and pretreatment NLR values. Because of a considerable high NPV, in the patients with higher NLR who had luminal type BC in which pCR is lower after NACT, such treatment may not be recommended.