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Nomogram to predict treatment outcome of fluoropyrimidine/platinum-based chemotherapy in metastatic esophageal squamous cell carcinoma.

ABSTRACT: The degree of benefit from palliative chemotherapy differs widely among patients with metastatic esophageal squamous cell carcinoma (MESCC). The purpose of this study was to develop and validate a prognostic nomogram to predict survival and aid physicians and patients in the decision-making process regarding treatment options.Clinicopathologic variables and treatment outcomes of 239 patients who were diagnosed with MESCC and received either fluorouracil/cisplatin (FP) or capecitabine/cisplatin (XP) as first-line chemotherapy were reviewed. A nomogram was developed as a prognostic scoring system incorporating significant clinical and laboratory variables based on a multivariate Cox proportional hazards regression model. An independent series of 61 MESCC patients treated with FP served as an independent data set for nomogram validation.No difference in response rate was observed between the FP group (44.8%) and the XP group (54.2%). Similarly, no significant differences in median progression-free survival and median overall survival were observed between regimen groups. Multivariate analysis showed that poor performance status (Eastern Cooperative Oncology Group [ECOG] status?2), weight loss (10% of the weight loss for 3 months), low albumin level (?3.5 g/dL), and absence of previous esophagectomy at the time of chemotherapy were significantly associated with low OS in both groups (p<0.05). Based on these findings, patients were classified into favorable (score, 0 to 90), intermediate (91-134), and poor (>135) prognostic groups. The median survival for those with a favorable ECOG was 13.8 months (95% confidence interval [CI], 10.8 to 18.6 months), for intermediate 11.2 months (95% CI, 8.7 to 11.9 months), and for poor, 7.0 months (95% CI, 3.6 to 10.0 months). External validation of the nomogram in a different patient cohort yielded significantly similar findings.The nomogram described here predicts survival in MESCC patients and could serve as a guide for the use of FP/XP chemotherapy in MESCC patients.

SUBMITTER: Jung HA

PROVIDER: S-EPMC3893326 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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Nomogram to predict treatment outcome of fluoropyrimidine/platinum-based chemotherapy in metastatic esophageal squamous cell carcinoma.

Jung Hyun Ae HA Adenis Antoine A Lee Jeeyun J Park Se Hoon SH Maeng Chi Hoon CH Park Silvia S Ahn Hee Kyung HK Shim Young Mog YM Penel Nicolas N Im Young-Hyuck YH

Cancer research and treatment 20131231 4

<h4>Purpose</h4>The degree of benefit from palliative chemotherapy differs widely among patients with metastatic esophageal squamous cell carcinoma (MESCC). The purpose of this study was to develop and validate a prognostic nomogram to predict survival and aid physicians and patients in the decision-making process regarding treatment options.<h4>Materials and methods</h4>Clinicopathologic variables and treatment outcomes of 239 patients who were diagnosed with MESCC and received either fluoroura ...[more]

PMID: 24454001

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Project description:BackgroundFit patients with metastatic urothelial carcinoma (mUC) receive first-line platinum-based combination chemotherapy (fPBC) as standard of care and may receive additional later-line chemotherapy after progression. Our study compares outcomes with subsequent platinum-based chemotherapy (sPBC) versus subsequent non-platinum-based chemotherapy (sNPBC).Materials and methodsPatients from 27 international centers in the Retrospective International Study of Cancers of the Urothelium (RISC) who received fPBC for mUC and at least two cycles of subsequent chemotherapy were included in this study. A multivariable Cox proportional hazards model compared overall survival (OS) and progression-free survival (PFS).ResultsOne hundred thirty-five patients received sPBC and 161 received sNPBC. Baseline characteristics were similar between groups, except patients who received sPBC had higher baseline hemoglobin, higher disease control rate with fPBC, and longer time since fPBC. OS was superior in the sPBC group (median 7.9 vs 5.5 months) in a model adjusting for comorbidity burden, performance status, liver metastases, number of fPBC cycles received, best response to fPBC, and time since fPBC (hazard ratio, 0.72; 95% confidence interval, 0.53-0.98; p = .035). There was no difference in PFS. More patients in the sPBC group achieved disease control than in the sNPBC group (57.4% vs 44.8%; p = .041). Factors associated with achieving disease control in the sPBC group but not the sNPBC group included longer time since fPBC, achieving disease control with fPBC, and absence of liver metastases.ConclusionAfter receiving fPBC for mUC, patients who received sPBC had better OS and disease control. This may help inform the choice of subsequent chemotherapy in patients with mUC.Implications for practicePatients with progressive metastatic urothelial carcinoma after first-line platinum-based combination chemotherapy may now receive immuno-oncology agents, erdafitinib, enfortumab vedotin, or sacituzumab govitecan-hziy; however, those ineligible for these later-line therapies or who progress after receiving them may be considered for subsequent chemotherapy. In this retrospective study of 296 patients, survival outcomes and disease control rates were better in those receiving subsequent platinum-based rechallenge compared with non-platinum-based chemotherapy, suggesting that patients should receive platinum rechallenge if clinically able. Disease control with platinum rechallenge was more likely with prior first-line platinum having achieved disease control, longer time since first-line platinum, and absence of liver metastases.

Project description:BackgroundAdjuvant chemotherapy in patients with resected esophageal squamous cell cancer (ESCC) remains controversial for its uncertain role in improving overall survival (OS). Nucleotide excision repair (NER) removes DNA-adducts in tumor cells induced by the platinum-based chemotherapy and thus may modulate efficacy of the treatment. The present study evaluated if single nucleotide polymorphisms (SNPs) of NER genes were prognostic biomarkers in ESCC patients treated with platinum-based adjuvant chemotherapy (PAC).MethodsThe analysis included 572 patients, for whom six SNPs of NER genes [i.e., XPC (rs1870134 and rs2228001), ERCC2/XPD rs238406 and ERCC5/XPG (rs2094258, rs2296147 and rs873601)] were detected with the TaqMan assay. Kaplan-Meier analyses and Cox proportional hazards models were used to evaluate their associations with disease free survival (DFS) and OS of these ESCC patients receiving PAC. Receiving operating characteristic curve analysis was used to evaluate the role of the risk genotypes in the DFS and OS.ResultsWe found that ERCC5/XPG rs2094258 and rs873601 and ERCC2/XPD rs238406 SNPs were independently associated with poorer DFS and OS of ESCC patients [ERCC5/XPG rs2094258: CT+TT vs. CC: adjusted hazards ratio (adjHR) = 1.68 and P = 0.012 for DFS; adjHR = 1.99 and P = 0.0001 for OS; ERCC5/XPG rs873601: GA+GG vs. AA: adjHR = 1.59 and P = 0.024 for DFS; adjHR = 1.91 and P = 0.0005 for OS; ERCC2/XPD rs238406: TT vs. GG+GT: adjHR = 1.43 and P = 0.020 for DFS; adjHR = 1.52 and P = 0.008 for OS]. These HRs increased as the number of risk genotypes increased in the combined analysis. The model combining the risk genotypes with clinical characteristics or the TNM stage system was better in predicting outcomes in ESCC patients with PAC.ConclusionSNPs of ERCC2/XPD and ERCC5/XPG may independently and jointly predict survival of ESCC patients treated with PAC in this study population. Further validation in other study populations is warranted.

Project description:The lymphovascular invasion (LVI) status facilitates the determination of the optimal therapeutic strategy for superficial esophageal squamous cell carcinoma (SESCC), but in clinical practice, LVI must be confirmed by postoperative pathology. However, studies of the risk factors for LVI in SESCC are limited. Consequently, this study aimed to identify the risk factors for LVI and use these factors to establish a prediction model. The data of 516 patients who underwent radical esophagectomy between January 2007 and September 2019 were retrospectively collected (training set, n=361, January 2007 to May 2015; validation set, n=155, June 2015 to September 2019). In the training set, least absolute shrinkage and selection operator (LASSO) regression and multivariate analyses were utilized to identify predictive factors for LVI in patients with SESCC. A nomogram was then developed using these predictors. The area under the curve (AUC), calibration curve, and decision curve were used to evaluate the efficiency, accuracy, and clinical utility of the model. LASSO regression indicated that the tumor size, depth of invasion, tumor differentiation, lymph node metastasis (LNM), sex, circumferential extension, the presence of multiple lesions, and the resection margin were correlated with LVI. However, multivariate analysis revealed that only the tumor size, depth of invasion, tumor differentiation, and LNM were independent risk factors for LVI. Incorporating these four variables, model 1 achieved an AUC of 0.817 in predicting LVI. Adding circumferential extension to model 1 did not appreciably change the AUC and integrated discrimination improvement, but led to a significant increase in the net reclassification improvement (p=0.011). A final nomogram was constructed by incorporating tumor size, depth of invasion, tumor differentiation, LNM, and circumferential extension and showed good discrimination (training set, AUC=0.833; validation set, AUC=0.819) and good calibration in the training and validation sets. Decision curve analysis demonstrated that the nomogram was clinically useful in both sets. Thus, it is possible to predict the status of LVI using this nomogram scoring system, which can aid the selection of an appropriate treatment plan.

Dataset Information

Nomogram to predict treatment outcome of fluoropyrimidine/platinum-based chemotherapy in metastatic esophageal squamous cell carcinoma.

Publications

Nomogram to predict treatment outcome of fluoropyrimidine/platinum-based chemotherapy in metastatic esophageal squamous cell carcinoma.

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