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Purpose@#The purpose of this phase II trial was to evaluate whether the addition of simvastatin, a synthetic 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, to preoperative chemoradiotherapy (CRT) with capecitabine confers a clinical benefit to patients with locally advanced rectal cancer (LARC). @*Materials and Methods@#Patients with LARC (defined by clinical stage T3/4 and/or lymph node positivity) received preoperative radiation (45-50.4 Gy in 25-28 daily fractions) with concomitant capecitabine (825 mg/m2 twice per day) and simvastatin (80 mg, daily). Curative surgery was planned 4-8 weeks after completion of the CRT regimen. The primary endpoint was pathologic complete response (pCR). The secondary endpoints included sphincter-sparing surgery, R0 resection, disease-free survival, overall survival, the pattern of failure, and toxicity. @*Results@#Between October 2014 and July 2017, 61 patients were enrolled; 53 patients completed CRT regimen and underwent total mesorectal excision. The pCR rate was 18.9% (n=10) by per-protocol analysis. Sphincter-sparing surgery was performed in 51 patients (96.2%). R0 resection was achieved in 51 patients (96.2%). One patient experienced grade 3 liver enzyme elevation. No patient experienced additional toxicity caused by simvastatin. @*Conclusion@#The combination of 80 mg simvastatin with CRT and capecitabine did not improve pCR in patients with LARC, although it did not increase toxicity.
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Purpose@#The optimal tumor mutational burden (TMB) value for predicting treatment response to programmed cell death-1 (PD-1) checkpoint inhibitors in advanced gastric cancer (AGC) remains unclear. We aimed to investigate the optimal TMB cutoff value that could predict the efficacy of PD-1 checkpoint inhibitors in AGC. @*Materials and Methods@#Patients with AGC who received pembrolizumab or nivolumab between October 1, 2020, and July 27, 2021, at Samsung Medical Center in Korea were retrospectively analyzed. The TMB levels were measured using a next-generation sequencing assay. Based on receiver operating characteristic curve analysis, the TMB cutoff value was determined. @*Results@#A total 53 patients were analyzed. The TMB cutoff value for predicting the overall response rate (ORR) to PD-1 checkpoint inhibitors was defined as 13.31 mutations per megabase (mt/Mb) with 56% sensitivity and 95% specificity. Based on this definition, 7 (13.2%) patients were TMB-high (TMB-H). The ORR differed between the TMB-low (TMB-L) and TMB-H (8.7% vs. 71.4%, P=0.001). The progression-free survival and overall survival (OS) for 53 patients were 1.93 (95% confidence interval [CI], 1.600–2.268) and 4.26 months (95% CI, 2.992–5.532). The median OS was longer in the TMB-H (20.8 months; 95% CI, 2.292–39.281) than in the TMB-L (3.31 months; 95% CI, 1.604–5.019; P=0.049). @*Conclusions@#The TMB cutoff value for predicting treatment response in AGC patients who received PD-1 checkpoint inhibitor monotherapy as salvage treatment was 13.31 mt/Mb.When applying the programmed death ligand-1 status to TMB-H, patients who would benefit from PD-1 checkpoint inhibitors can be selected.
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Background@#Pediatric nasal fractures, unlike adult nasal fractures, are treated surgically as early as 7 days after the initial trauma. However, in some cases, a week or more elapses before surgery, and few studies have investigated the consequences of delayed surgery for pediatric nasal fractures. The purpose of this study was to evaluate the postoperative outcomes of pediatric nasal fractures according to the time interval between the initial trauma and surgery. @*Methods@#The records of pediatric patients under 12 years old who underwent closed reduction of nasal bone fracture from March 2012 to February 2020 were reviewed. The interval between trauma and surgery was divided into within 7 days (early reduction) and more than 7 days (delayed reduction). Postoperative results were classified into five grades (excellent, good, moderate, poor, and very poor) based on the degree of reduction shown on computed tomography. @*Results@#Ninety-eight patients were analyzed, of whom 51 underwent early reduction and 47 underwent delayed reduction. Forty-two (82.4%) of the 51 patients in the early reduction group showed excellent results, and nine (17.6%) showed good results. Thirty-nine (83.0%) of the 47 patients in the delayed reduction group showed excellent results and eight (17.0%) showed good results. No statistically significant difference in outcomes was found between the two groups (chi-square test p= 0.937). However, patients without septal injury were significantly more likely to have excellent postoperative outcomes (chi-square test p< 0.01). @*Conclusion@#No statistically significant difference was found in the outcomes of pediatric nasal fractures between the early and delayed reduction groups. Successful surgical results were found even in patients who received delayed reduction (more than 7 days after trauma).
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Background@#Pediatric nasal fractures, unlike adult nasal fractures, are treated surgically as early as 7 days after the initial trauma. However, in some cases, a week or more elapses before surgery, and few studies have investigated the consequences of delayed surgery for pediatric nasal fractures. The purpose of this study was to evaluate the postoperative outcomes of pediatric nasal fractures according to the time interval between the initial trauma and surgery. @*Methods@#The records of pediatric patients under 12 years old who underwent closed reduction of nasal bone fracture from March 2012 to February 2020 were reviewed. The interval between trauma and surgery was divided into within 7 days (early reduction) and more than 7 days (delayed reduction). Postoperative results were classified into five grades (excellent, good, moderate, poor, and very poor) based on the degree of reduction shown on computed tomography. @*Results@#Ninety-eight patients were analyzed, of whom 51 underwent early reduction and 47 underwent delayed reduction. Forty-two (82.4%) of the 51 patients in the early reduction group showed excellent results, and nine (17.6%) showed good results. Thirty-nine (83.0%) of the 47 patients in the delayed reduction group showed excellent results and eight (17.0%) showed good results. No statistically significant difference in outcomes was found between the two groups (chi-square test p= 0.937). However, patients without septal injury were significantly more likely to have excellent postoperative outcomes (chi-square test p< 0.01). @*Conclusion@#No statistically significant difference was found in the outcomes of pediatric nasal fractures between the early and delayed reduction groups. Successful surgical results were found even in patients who received delayed reduction (more than 7 days after trauma).
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Purpose@#The purpose of this study was to investigate the role of carcinoembryonic antigen (CEA) levelsin improving the performance of magnetic resonance imaging (MRI) for the predictionof pathologic response after the neoadjuvant chemoradiation (NCRT) for patients with rectalcancer. @*Materials and Methods@#We retrospectively reviewed the medical records of 524 rectal cancer patients who underwentNCRT and total mesorectal excision between January 2009 and December 2014. Theperformances of MRI with or without CEA parameters (initial CEA and CEA dynamics) forprediction of pathologic tumor response grade (pTRG) were compared by receiver-operatingcharacteristic analysis with DeLong’s method. Cox regression was used to identify the independentfactors associated to pTRG and disease-free survival (DFS) after NCRT. @*Results@#The median follow-up was 64.0 months (range, 3.0 to 113.0 months). On multivariate analysis,poor tumor regression grade on MRI (mrTRG; p < 0.001), initial CEA (p < 0.001) andthe mesorectal fascia involvement on MRI before NCRT (mrMFI; p=0.054) showed associationwith poor pTRG. The mrTRG plus CEA parameters showed significantly improved performancesin the prediction of pTRG than mrTRG alone. All of mrTRG, mrMFI, and initial CEAwere also identified as independent factors associated with DFS. The initial CEA further discriminatedDFS in the subgroups with good mrTRG or that without mrMFI. @*Conclusion@#The CEA parameters significantly improved the performance of MRI in the prediction ofpTRG after NCRT for patients with rectal cancer. The DFS was further discriminated by initialCEA level in the groups with favorable MRI parameters.
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Background@#The standard treatment of nasal bone fractures in pediatric patients is closed reduction. Conservative treatment is sometimes performed, but poses a risk of nasal deformity. The aim of this study was to evaluate the outcomes of bone remodeling in pediatric nasal fractures. @*Methods@#Information was extracted from the medical records of patients under 12 years of age who received conservative treatment for a nasal bone fracture and underwent follow-up computed tomography (CT) examinations. The initial fracture and its outcomes over time were graded as excellent, good, or fair according to the malalignment, displacement, or irregularity of the fractured segments. The outcomes of remodeling were evaluated through changes in the grade of the fracture between initial and subsequent CT scans. @*Results@#The review identified 16 patients between March 2015 and December 2019. Their mean age was 6.2 years, and the average follow-up period was 4.9 months. Three of the five patients with a plane I frontal impact showed improved outcomes of remodeling from good to excellent, and the remaining two patients, improved from fair to good. Eight of the 11 patients with plane I lateral impacts showed improved outcomes, from good to excellent, while one patient, improved from fair to good, one patient, improved from fair to excellent, and one patient showed no interval changes. @*Conclusion@#In 15 of these 16 patients with non-severe fractures, the bony contour improved through remodeling, without surgical intervention. Therefore, we suggest that conservative treatment is a feasible option for mild pediatric nasal fractures.
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Background@#Endoscopic forehead lift effectively corrects brow ptosis, and is less invasive and has fewer complications than classic forehead lift. Therefore, endoscopic procedures are often used instead of making a coronal incision. However, very few studies have investigated changes in the height of the hairline and documented exact values regarding the extent of forehead elongation after these procedures. Therefore, we conducted this study to determine the degree to which the height of the forehead changes after endoscopic forehead lift. @*Methods@#Patients’ medical records were retrospectively analyzed and measurements of clinical photography were made to investigate changes in the height of the forehead after the procedure. Subjects were divided into an experimental group (n=33) and an age-matched control group (n=33) for analysis; the experimental group comprised those who underwent endoscopic forehead lift from January 2015 to March 2018, and the control group comprised those who underwent upper blepharoplasty without forehead rejuvenation from July 2009 to September 2017. @*Results@#The changes between the preoperative and postoperative height of the forehead in the experimental group were not statistically significant (right, P=0.163; left, P=0.256; midline, P=0.545). However, the changes in the height of the forehead in the control group were statistically significant on the right side (P=0.026) and left side (P=0.028), but not at the midline (P=0.244). @*Conclusions@#We investigated the extent of forehead elongation that occurred in cases of endoscopic forehead lift and verified that significant forehead height changes did not occur after endoscopic forehead lift.
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PURPOSE: The purpose of this study was to compare prognostic differentiation performances of the 7th and the 8th edition of American Joint Committee on Cancer (AJCC) staging system for gastric cancer (GC) patients. MATERIALS AND METHODS: A total of 1,633 GC patients who underwent curative D2 resection followed by adjuvant chemotherapy alone (CA) or concurrent chemo-radiotherapy (CCRT) from 2004 to 2013 were included. Concordance index (c-index) was applied to compare the discriminatory ability. RESULTS: In the 8th edition, migration of stage was detected in 248 patients (15.2%). Among them, 121 patients were up-staged while 127 patients were down-staged. Overall, there was no statistically significant difference in the discriminatory ability between the 7th and 8th editions. The new edition of staging system, however, showed a trend of better prognostic performance not only in recurrence-free survival (c-index=0.734; 95% confidence interval [CI], 0.706 to 0.762 in the 7th edition vs. c-index=0.740; 95% CI, 0.712 to 0.768 in the 8th edition; p=0.14), but also in overall survival (c-index=0.717; 95% CI, 0.688 to 0.745 in the 7th edition vs. c-index=0.722; 95% CI, 0.694 to 0.751 in the 8th edition; p=0.19), especially in stage III. This finding was repeated in the subgroup analysis regardless of adjuvant CA or CCRT. CONCLUSION: Generally, the 8th edition of AJCC staging system had failed to show a superior discriminatory ability for curatively D2 resected GC patients than the 7th edition, although there was a trend of better prognostic performance of the new edition, regardless of adjuvant treatment method.
Subject(s)
Humans , Chemotherapy, Adjuvant , Joints , Methods , Neoplasm Staging , Prognosis , Radiotherapy , Recurrence , Stomach NeoplasmsABSTRACT
PURPOSE: Simvastatin has demonstrated anti-tumor activity in preclinical studies via tumor cell senescence, apoptosis, and anti-angiogenesis. This phase II trial evaluated the efficacy and toxicity profile of conventional XELOX and bevacizumab chemotherapy plus simvastatin in metastatic colorectal cancer patients (MCRC). MATERIALS AND METHODS: Patients with MCRC received first-line XELOX in 3-week treatment cycles of intravenous oxaliplatin 130 mg/m² plus bevacizumab 7.5 mg/kg (day 1), followed by oral capecitabine 1,000 mg/m² twice daily (day 1-14). Simvastatin 80 mg tablets were taken orally once daily every day during the period of chemotherapy. The primary endpoint was progression-free survival (PFS). Secondary endpoints were response rate, duration of response, overall survival (OS), time to progression, and toxicity. RESULTS: From January 2014 to April 2015, 60 patients were enrolled and 55 patients were evaluable for tumor response. The median follow-up duration was 30.1 months (range, 28.5 to 31.7 months). The median PFS was 10.4 months (95% confidence interval [CI], 9.6 to 11.1). The median OS of all patients was 19.0 months (95% CI, 11.9 to 26.0). The disease-control rate and overall response rate were 88.3% (95% CI, 74 to 96) and 58.3% (95% CI, 44 to 77), respectively, by intent-to-treat protocol analysis. There was one complete response and 34 partial responses. One patient experienced grade 3 creatine kinase elevation and liver enzyme elevation. CONCLUSION: Based on the current study, the addition of 80 mg simvastatin to XELOX and bevacizumab showed comparable clinical efficacy in patients with MCRC as first-line chemotherapy and did not increase toxicity.
Subject(s)
Humans , Apoptosis , Arm , Bevacizumab , Capecitabine , Cellular Senescence , Colorectal Neoplasms , Creatine Kinase , Disease-Free Survival , Drug Therapy , Follow-Up Studies , Liver , Simvastatin , Tablets , Treatment OutcomeABSTRACT
PURPOSE: Gastric cancer shows a male predominance that might be explained by protective effects from estrogens in females. Two Lauren classification histological subtypes, intestinal and diffuse, have distinct carcinogeneses. The purpose of this study was to estimate the effects of sex hormone on female gastric cancer according to Lauren classification. MATERIALS AND METHODS: We reviewed medical records for and administered questionnaires, surveying reproductive and hormonal factors, to 758 patients who underwent gastrectomy for gastric cancer at Samsung Medical Center from May 2012 to November 2014. Clinicopathological characteristics were compared between females and males. The incidence of intestinal-type gastric cancer was compared between females subgroups, consist of premenopausal women and three groups of postmenopausal women (five-year intervals after menopause), and males. The association between reproductive factors and intestinal-type gastric cancer was analyzed by multivariate models for the female group. RESULTS: In total, 227 females (29.9%) and 531 males (70.9%) were included in the analysis. Undifferentiated adenocarcinoma and diffuse-type histology were more frequent in female patients than male patients. While 221 (41.6%) male patients had intestinal-type gastric cancer, no premenopausal female patient had this type of gastric cancer. The incidence of intestinal-type gastric cancer increased with time after menopause, and was similar to males after 10 years from menopause. Parity was associated with an increased risk of intestinal-type gastric cancer in menopausal women. CONCLUSION: These findings support that female sex hormones might be protective against intestinal-type gastric cancer.
Subject(s)
Female , Humans , Male , Middle Aged , Adenocarcinoma/pathology , Multivariate Analysis , Postmenopause , Protective Agents/metabolism , Reproduction , Risk Factors , Stomach Neoplasms/pathology , Stomach Neoplasms/surgeryABSTRACT
PURPOSE: We aimed to discuss the roles of radiation and chemotherapy as adjuvant treatment in patients with staged IB GC who were enrolled in the adjuvant chemoradiotherapy in stomach tumors (ARTIST) trial. MATERIALS AND METHODS: Among the 458 patients who were enrolled in the ARTIST trial, 99 had stage IB disease. The patients were randomly assigned to receive either adjuvant chemoradiotherapy with capecitabine plus cisplatin (XP, n=50) or chemoradiotherapy (XPRT, n=49). Survival analyses were performed in accordance with the AJCC 2010 staging system. RESULTS: According to the AJCC 2010 system, stage migration from IB to II occurred in 71% of the patients; 98% of the T2 N0 cases were reclassified as T3 N0, and 42% of the T1 N1 cases were reclassified as T1 N2. When comparing survival outcomes between the XPRT and XP arms for stage IB cancer (AJCC 2002), no significant difference in 5-year disease-free survival (DFS) between the 2 arms was found. (median 5-year DFS, not reached, P=0.256). The patients classified as having stage IB cancer (AJCC 2002) and reclassified as having stage II cancer (AJCC 2010) exhibited worse prognoses than those who remained in stage IB, although the difference was not statistically significant (5-year DFS rate, 83% vs. 93%). When we compared 5-year DFS in 70 patients with stage II (AJCC 2010), the addition of radiotherapy to XP chemotherapy did not show better outcome than XP alone (P=0.137). CONCLUSIONS: The role of adjuvant chemoradiotherapy in the treatment of stage IB GC (AJCC 2002) warrants further investigation.
Subject(s)
Humans , Arm , Capecitabine , Chemoradiotherapy , Chemoradiotherapy, Adjuvant , Chemotherapy, Adjuvant , Cisplatin , Disease-Free Survival , Drug Therapy , Prognosis , Radiotherapy , Stomach Neoplasms , StomachABSTRACT
PURPOSE: Chromogranin A (CgA) has been considered to be valuable not only in the diagnosis but also in monitoring the disease response to treatment. However, only a few studies have been published on this issue. We purposed to evaluate whether biochemical response using plasma CgA level is reliable in concordance with the clinical response of grade 1-3 nonfunctiong gastroenteropancreatic neuroendocrine tumors (GEP-NETs). MATERIALS AND METHODS: Between March 2011 and September 2013, a total of 27 cases in 18 patients were analysed, clinically and radiologically while serial CgA tests were also conducted during treatment. Tumor responses were defined by both Response Evaluation Criteria in Solid Tumors (RECIST) criteria ver. 1.1 and biochemical criteria based on the CgA level. RESULTS: Among the 27 cases analysed, no difference in the basal CgA level was observed with regard to gender, primary tumor site, tumor grade (World Health Organization classification), liver metastasis, number of metastatic site, and line of chemotherapy. The overall response rate (RR) by RECIST criteria ver. 1.1 was six out of the 27 cases (22.2%) and eight out of the 27 cases (29.6%) for biochemical RR. The overall concordance rates of the response based on RECIST and biochemical criteria were 74%. In grades 1 and 2 GEP-NETs (n=17), the concordance rate of the disease control was 94.1%. There was a significant difference for progression-free survival (PFS) between responders and non-responder in accordance to biochemical criteria (35.73 months vs. 5.93 months, p=0.05). CONCLUSION: This study revealed that changes of the plasma CgA levels were associated with tumour response. Additionally, biochemical response based on serial CgA may be a predictive marker for PFS in GEP-NETs.
Subject(s)
Humans , Chromogranin A , Diagnosis , Disease-Free Survival , Drug Therapy , Liver , Neoplasm Metastasis , Neuroendocrine Tumors , PlasmaABSTRACT
PURPOSE: While the Trastuzumab for Gastric Cancer (ToGA) trial demonstrated the efficacy and safety of trastuzumab-based chemotherapy in HER2-positive metastatic gastric cancer, the overall survival (OS) benefit was not found in Asian and diffuse-type cancer patients. The aim of the study is to investigate predictive markers for trastuzumab-based chemotherapy. MATERIALS AND METHODS: Data of patients with HER2-positive gastric cancer treated with trastuzumab-based chemotherapy were analyzed retrospectively. RESULTS: A total of 168 Asian patients were included. The median age was 60 years (range, 27 to 85 years) and the male:female ratio was 118 (70.2%):50 (29.8%). Fourteen (8.3%), 63 (37.5%), 75 (44.6%), and 11 (6.5%) patients had well, moderately, poorly-differentiated tubular adenocarcinoma and signet ring cell carcinoma, respectively. With 14 complete responses and 73 partial responses, the response rate was 50.6%. The median progression-free survival (PFS) was 10.2 months (95% confidence interval [CI], 8.7 to 11.7), and the median OS was 18.5 months (95% CI, 16.4 to 50.6). Next, we investigated the effect of poorly-differentiated histology (PDH, poorly-differentiated tubular adenocarcinoma+signet ring cell carcinoma) on clinical outcomes. The median PFS (8.9 months vs. 11.5 months, p=0.16) was slightly inferior in PDH patients, and the median OS was significantly shorter in PDH patients (14.6 months vs. 19.0 months, p=0.025). CONCLUSION: While subset analysis of the ToGA trial demonstrated that trastuzumab-based chemotherapy may not be beneficial for Asians and patients with PDH, our data may suggest that even in Asian patients and patients with PDH, trastuzumab-based chemotherapy could be associated with improved clinical outcomes in patients with HER2-positive gastric cancer.
Subject(s)
Humans , Adenocarcinoma , Asian People , Carcinoma, Signet Ring Cell , Disease-Free Survival , Drug Therapy , Ethnicity , Receptor, ErbB-2 , Retrospective Studies , Stomach NeoplasmsABSTRACT
PURPOSE: In the Adjuvant Chemoradiotherapy in Stomach Tumors (ARTIST) trial, we investigated whether chemoradiotherapy after D2 gastrectomy reduces the rate of recurrence. Recently, the ratio of metastatic lymph nodes to examined lymph nodes (N ratio) has been proposed as an independent prognostic factor in gastric cancer (GC). The aim of this study was to investigate the relationship between the metastatic N ratio and prognosis of GC after curative D2 surgery. MATERIALS AND METHODS: We retrospectively reviewed the data of 458 ARTIST patients who underwent D2 gastrectomy followed by adjuvant chemotherapy (XP, n=228) or chemoradiotherapy (XPRT, n=230). The disease-free survival (DFS) rates of patients were used to evaluate the influence of N ratio on the treatment outcome. To achieve this, 4 different N ratio categories (0%, 1%~9%, 10%~25%, and >25%) were compared on the basis of their influence on the treatment outcome. RESULTS: On multivariate analysis, the N ratio remained an independent prognostic factor for DFS. The hazard ratios (HRs) for the N ratio categories of 0%, 1%~9%, 10%~25%, and >25% were 1, 1.061, 1.202, and 3.571, respectively. In patients having N ratio >25%, the 5-year DFS rates were 55% and 28% for the XPRT and XP arms, respectively (HR, 0.527; 95% confidence interval, 0.307~0.904; P=0.020). CONCLUSIONS: In patients with curatively resected GC, the N ratio was independently associated with DFS. Although this finding warrants further investigation in future prospective studies, the benefit of chemoradiotherapy for D2 resected GC appears to be more beneficial in cancers having N ratios >25%.
Subject(s)
Humans , Arm , Chemoradiotherapy , Chemoradiotherapy, Adjuvant , Chemotherapy, Adjuvant , Disease-Free Survival , Gastrectomy , Lymph Nodes , Multivariate Analysis , Prognosis , Prospective Studies , Recurrence , Retrospective Studies , Stomach Neoplasms , Stomach , Treatment OutcomeABSTRACT
PURPOSE: A prospective phase II trial was conducted to evaluate the effectiveness and toxicity of regional hyperthermia and whole liver irradiation (WLI) for numerous chemorefractory liver metastases from colorectal cancer. MATERIALS AND METHODS: Enrolled patients had numerous chemorefractory hepatic metastases from colorectal cancer. Five sessions of hyperthermia and seven fractions of 3-gray WLI were planned. Health-related quality of life (HRQoL) was determined using the Korean version of the European Organization for Research and Treatment of Cancer quality of life questionnaire C-30 and the Functional Assessment of Cancer Therapy-Hepatobiliary version 4.0. Objective and pain response was evaluated. RESULTS: A total of 12 patients consented to the study and the 10 who received WLI and hyperthermia were analyzed. WLI was completed as planned in nine patients and hyperthermia in eight. Pain response was partial in four patients and stable in four. Partial objective response was achieved in three patients (30.0%) and stable disease was seen in four patients at the 1-month follow-up. One patient died 1 month after treatment because of respiratory failure related to pleural metastasis progression. Other grade III or higher toxicities were detected in three patients; however, all severe toxicities were related to disease progression rather than treatment. No significant difference in HRQoL was noted at the time of assessment for patients who were available for questionnaires. CONCLUSION: Combined WLI and hyperthermia were well tolerated without severe treatment-related toxicity with a promising response from numerous chemorefractory hepatic metastases from colorectal cancer.
Subject(s)
Humans , Colorectal Neoplasms , Disease Progression , Fever , Follow-Up Studies , Hyperthermia, Induced , Liver , Neoplasm Metastasis , Prospective Studies , Quality of Life , Radiotherapy , Respiratory InsufficiencyABSTRACT
PURPOSE: Capecitabine is known to increase mean corpuscular volume (MCV). To define the incidence of capecitabine-induced macrocytosis and its association with chemotherapy outcomes, we investigated data of 89 patients with advanced gastric cancer (AGC) who were enrolled in a randomized chemotherapy trial involving capecitabine. MATERIALS AND METHODS: Chemotherapy-naive AGC patients were treated with capecitabine (1,000 mg/m2/day on days 1-14) plus cisplatin (75 mg/m2 on day 1), with or without epirubicin (50 mg/m2 on day 1). Complete blood counts including MCV were measured at baseline and on day 1 of each 3-week chemotherapy course. Macrocytosis was defined as a MCV increase > 10 fL from baseline. Multivariate Cox proportional hazards models were used for analysis of the impact of clinical and MCV values on chemotherapy outcomes. RESULTS: At baseline, the mean MCV was 88.2 fL (normal range, 80 to 100 fL). During chemotherapy, MCV increased in a dose-dependent manner with a mean increase of 11.3 fL. MCV elevation after capecitabine treatment in 74 patients (90%) and 44 patients (42%) developed macrocytosis. RESULTS: of multivariate analysis showed that development of macrocytosis was independent of baseline hemoglobin level, liver metastasis, performance status, or liver function. The number of chemotherapy cycles showed strong association with development of macrocytosis and hematologic adverse events. In addition, a significant association was observed between macrocytosis and clinical response or survival. CONCLUSION: Macrocytosis developed with more frequent and prolonged use of capecitabine. It is possible that association with treatment outcomes warrants further investigation.
Subject(s)
Humans , Blood Cell Count , Cisplatin , Drug Therapy , Epirubicin , Erythrocyte Indices , Incidence , Liver , Multivariate Analysis , Neoplasm Metastasis , Proportional Hazards Models , Stomach NeoplasmsABSTRACT
PURPOSE: To determine the prognostic and predictive value of liver volume in colorectal cancer patients with unresectable liver metastases. MATERIALS AND METHODS: Sixteen patients received whole liver radiotherapy (WLRT) between January 1997 and June 2013. A total dose of 21 Gy was delivered in 7 fractions. RESULTS: The median survival time after WLRT was 9 weeks. In univariate analysis, performance status, serum albumin and total bilirubin level, liver volume and extrahepatic metastases were associated with survival. The mean liver volume was significantly different between subgroups with and without pain relief (3,097 and 4,739 mL, respectively; p = 0.002). CONCLUSION: A larger liver volume is a poor prognostic factor for survival and also a negative predictive factor for response to WLRT. If patients who are referred for WLRT have large liver volume, they should be informed of the poor prognosis and should be closely observed during and after WLRT.
Subject(s)
Humans , Bilirubin , Colorectal Neoplasms , Liver , Neoplasm Metastasis , Prognosis , Radiotherapy , Serum Albumin , Tumor BurdenABSTRACT
PURPOSE: Fluoropyrimidine-based combination chemotherapy, in combination with either oxaliplatin or irinotecan, has demonstrated efficacy and tolerability in treatment of advanced colorectal cancer (ACC). MATERIALS AND METHODS: Between January 2006 and December 2007, a total of 478 ACC patients were treated with combination chemotherapy in first-line settings. Combination therapies included: 5-fluorouracil, folinic acid plus oxaliplatin (FOLFOX, n=172), 5-fluorouracil, folinic acid plus irinotecan (FOLFIRI, n=95), capecitabine plus oxaliplatin (XELOX, n=155), and capecitabine plus irinotecan (XELIRI, n=56). FOLFOX and FOLFIRI were repeated every 2 weeks, whereas XELOX and XELIRI were repeated every 3 weeks until occurrence of disease progression or unacceptable toxicity, or until a patient chose to discontinue treatment. RESULTS: The median age was 58 years (range, 19 to 84 years) and the median chemotherapy durations for FOLFOX, FOLFIRI, XELOX, and XELIRI were 4.9, 4.5, 5.7, and 5.4 months, respectively. Combination chemotherapy regimens were generally well tolerated. The estimated median progression-free-survival (PFS) for all patients was 6.8 months (95% confidence interval, 6.3 to 7.3 months). No statistically significant difference in PFS was found among regimens used as first-line chemotherapy. Sixty percent (n=290) of patients received second or further lines of therapy after failure. CONCLUSION: Fluoropyrimidine-based combination chemotherapy regimens appear to be equally active and tolerable as first-line therapy for ACC.
Subject(s)
Humans , Antineoplastic Combined Chemotherapy Protocols , Camptothecin , Colonic Neoplasms , Colorectal Neoplasms , Deoxycytidine , Disease Progression , Drug Therapy, Combination , Fluorouracil , Leucovorin , Organoplatinum Compounds , Retrospective StudiesABSTRACT
PURPOSE: The aim of this study was to determine whether the ERCC1 expression is effective to predict the clinical outcomes of patients with advanced gastric cancer (AGC) and who were treated with cisplatin-based first-line chemotherapy. MATERIALS AND METHODS: A total of 89 measurable AGC patients received cisplatin and capecitabine, with or without epirubicin, as a part of a randomized phase II study. Patients were included for the current molecular analysis if they had received two or more cycles of chemotherapy, their objective tumor responses were measured and if their paraffin-embedded tumor samples were available. The ERCC1 expression was examined by performing immunohistochemical (IHC) staining, and the patients were divided into two groups (positive or negative) according to the presence of IHC staining of the tumor cell nuclei. RESULTS: Of the 32 eligible patients, 21 patients (66%) had tumor with a positive expression of ERCC1 and the remaining 11 patients had tumor with a negative ERCC1-expression. The ERCC1-negative patients achieved a higher response rate than that of the ERCC1-positive patients (44% vs. 28%, respectively), although the difference was not statistically significant (p=0.42). The median survival time for the all patients was 14.6 months (95% CI: 13.6 to 15.6 months). The one-year survival rate was similar for the ERCC1-negative patients (61%) and the ERCC1-positive patients (70%). CONCLUSION: In the current study, the tumor ERCC1 expression by IHC staining could not predict the clinical response or survival of AGC patients who were treated with cisplatin-based first-line chemotherapy. The ERCC1 protein expression does not appear to be a useful tool for the selection of tailored chemotherapy for these patients.
Subject(s)
Humans , Cell Nucleus , Cisplatin , Deoxycytidine , Epirubicin , Fluorouracil , Stomach Neoplasms , Survival Rate , CapecitabineABSTRACT
PURPOSE: Oxaliplatin-induced chronic peripheral neurotoxicity (OXCPN) manifests as a loss of sensation and dysesthesia in the distal extremities, which may impair daily activities and increase in incidence with the amount of oxaliplatin delivered. The variation in the reported incidence and severity of OXCPN may be a consequence of differences in the baseline characteristics of patients. MATERIALS AND METHODS: This was a prospective study (ClinicalTrials.gov, NCT00977717) in which OXCPN was recorded for all consecutive colon cancer patients treated at Samsung Medical Center (Seoul, Korea) with oxaliplatin-based combination chemotherapy. The primary endpoint was the incidence of severe OXCPN (grade 2 lasting for >7 days, or grade 3). The association of severe OXCPN and pretreatment parameters was evaluated using a multivariate regression model. RESULTS: Between Jan 2008 and Feb 2010, 100 patients treated with adjuvant folinic acid/fluorouracil plus oxaliplatin (FOLFOX) and 266 patients treated with capecitabine plus oxaliplatin (XELOX) or FOLFOX for advanced disease were registered into our study. The median cumulative dose of oxaliplatin was 796 mg/m2 (range, 85 to 1,583 mg/m2). Severe OXCPN was observed in 126 (34%) patients. Overall, 43 patients discontinued chemotherapy due to toxicity: 23 without severe OXCPN and 20 with severe OXCPN. In univariate analysis, severe OXCPN was frequently observed in patients with age > or =55 years (p<0.01), stage II or III (p<0.01), adjuvant setting (p=0.01), FOLFOX (p<0.01), performance status of 0 (p=0.02), and those with no prior chemotherapy (p<0.01). In a multivariate regression model, the number of chemotherapy cycles and the cumulative oxaliplatin dose were not associated with the development of severe OXCPN. CONCLUSION: We failed to find a significant association between patient characteristics at baseline and the development of severe OXCPN after oxaliplatin-based combination chemotherapy. Pharmacogenomic profiling using genome-wide association study in these patients is underway.