The effect of change in PSA velocity on overall survival (OS) in men with biochemically recurrent prostate cancer (BRPC) treated with nonhormonal agents: Combined analysis of four phase 2 trials.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 121-121
Author(s):  
Daniel L. Suzman ◽  
Marianna Zahurak ◽  
Michael Anthony Carducci ◽  
Mario A. Eisenberger ◽  
Emmanuel S. Antonarakis
Keyword(s):  
Overall Survival ◽  
Cox Regression ◽  
Phase 2 ◽  
Cox Regression Analysis ◽  
Psa Kinetics ◽  
Investigational Drugs ◽  
Psa Velocity ◽  
Prospective Trials ◽  
The Impact ◽  
Baseline Psa

121 Background: A number of phase 2 trials in men with BRPC have assessed the impact of non-hormonal agents on PSA kinetics. We have previously demonstrated that changes in PSA kinetics are correlated with metastasis-free survival; however, it is unknown whether these changes may also correlate with overall survival (OS). Methods: We performed a combined retrospective analysis of 146 men with BRPC treated on phase 2 trials using one of four investigational drugs: lenalidomide (n=60), marimastat (n=39), ATN-224 (n=22), and imatinib (n=25). We examined factors influencing OS, including within-subject changes in PSA kinetics (PSA slope, PSA doubling time, and PSA velocity) before and 6 months after treatment initiation. Results: After a median follow up of 77 months, 47 men had died. In univariate Cox regression analysis, four factors were associated with OS: prior androgen deprivation therapy (ADT), prior local radiotherapy, baseline PSA velocity, and change in PSA velocity after therapy. In a landmark multivariable model, stratified by study, which also controlled for age and Gleason score (<7 vs ≥7): prior radiotherapy, baseline PSA velocity, and increase in PSA velocity remained independent predictors of OS (Table). Median OS for men with an increase in PSA velocity on treatment was 9.1 years vs 12.3 years for men with a decrease in PSA velocity (HR 1.95; 95%CI 1.07–3.57; P=0.03). Conclusions: This hypothesis-generating study suggests that within-subject changes in PSA velocity after initiation of non-hormonal therapy may correlate with OS in men with BRPC. If validated in prospective trials using OS as the primary endpoint, change in PSA velocity may represent a reasonable intermediate endpoint for screening new agents in these patients. [Table: see text]

The predictive value of MAP2K1/2 mutations for efficiency of immunotherapy in melanoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21587-e21587
Author(s):  
Ting Ye ◽  
Jieying Zhang ◽  
Xinyi Liu ◽  
Mengmei Yang ◽  
Yuhan Zhou ◽  
...  
Keyword(s):  
Overall Survival ◽  
Predictive Value ◽  
Cox Regression ◽  
Treatment Options ◽  
Objective Response ◽  
Progression Free Survival ◽  
Driver Mutations ◽  
Cox Regression Analysis ◽  
Melanoma Patients ◽  
The Impact

e21587 Background: Immunotherapies targeting immune checkpoint receptors have become the cornerstone of systemic treatment options for malignant melanoma. The response to these immunotherapies may correlate with driver mutations. MAP2K1/2 genes are mutated in approximately 10% of melanomas, however, the impact of MAP2K1/2 gene alterations on the efficiency of immunotherapy has not been clarified. Methods: Six metastatic melanoma clinical cohorts treated with ICIs were included to investigate the association between clinical efficacy of immunotherapy and MAP2K1/2 mutations. Survival analyses were conducted in cohorts receiving two kinds of ICB agents, namely anti-CTLA-4 or anti-PD-1. RNA expression profiling from these cohorts and from the TCGA melanoma cohort were used to explore the potential mechanism related to immune activation. Results: In an independent anti-CTLA-4-treated cohort (n = 110), we found that MAP2K1/2 mutations are predictive of high objective response rate (17.6% vs 1.3%, p = 0.0185) and long progression-free survival [median OS, 49.2 months vs 8.3 months; hazard ratio (HR) = 0.37; 95% CI, 0.15–0.91; p = 0.0307] and overall survival (median PFS, 19.4 months vs 2.8 months; HR = 0.2; 95% CI, 0.05–0.83; p = 0.0262). This predictive value was further validated in a pooled anti-CTLA-4-treated cohort (n = 235) in terms of overall survival (median OS, 49.3 months vs 22.0 months; HR = 0.44; 95% CI, 0.22–0.91; p = 0.0255). However, no correlation between MAP2K1/2 mutations and overall survival was observed in the anti-PD-1-treated cohort (n = 285). Subgroup Cox regression analysis indicated that MAP2K-mutated patients receive less benefit from the anti-PD-1 monotherapy than from the anti-CTLA-4 treatment (median OS, 27.0 months vs 49.3 months; HR = 3.26; 95% CI, 1.18–9.02; p = 0.0225), which was contrary to the result obtained for the total population. Furthermore, transcriptome profiling analysis revealed that MAP2K-mutated tumors are enriched in CD8+ T cells, B cells, and neutrophil cells and also express high levels of CD33 and IL10, which might be the underlying mechanism for melanoma patients with MAP2K1/2-mutated benefit more from anti-CTLA-4 treatment. Conclusions: We identified mutations in MAP2K1/2 genes as the independent predictive factors for anti-CTLA-4 therapy in melanoma patients and found that anti-CTLA-4 treatment in patient harbouring MAP2K1/2 mutations might be more effective than the anti-PD-1 therapy.

scholarly journals Distant survival for patients undergoing surgery using volatile versus IV anesthesia for hepatocellular carcinoma with portal vein tumor thrombus: a retrospective study

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Xiao-Yan Meng ◽  
Xiu-Ping Zhang ◽  
Zhe Sun ◽  
Hong-Qian Wang ◽  
Wei-Feng Yu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Portal Vein ◽  
Tumor Thrombus ◽  
Cox Regression ◽  
Cancer Recurrence ◽  
Portal Vein Tumor Thrombus ◽  
Cox Regression Analysis ◽  
The Impact ◽  
Underlying Pathophysiology

Abstract Background Whether anesthesia type is associated with the surgical outcome of Hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) remains to be determined. This study aims to investigate the impact of volatile inhalational anesthesia (INHA) versus total IV anesthesia (TIVA) on the survival outcomes in HCC patients with PVTT. Methods A cohort of in-patients whom were diagnosed of HCC with PVTT in Eastern Hepatobiliary Surgery Hospital, Shanghai, China, from January 1, 2008 to December 24, 2012 were identified. Surgical patients receiving the INHA and TIVA were screened out. The overall survival (OS), recurrence-free survival (RFS) and several postoperative adverse events were compared according to anesthesia types. Results A total of 1513 patients were included in this study. After exclusions are applied, 263 patients remain in the INHA group and 208 in the TIVA group. Patients receiving INHA have a lower 5-year overall survival rate than that of patients receiving TIVA [12.6% (95% CI, 9.0 to 17.3) vs. 17.7% (95% CI, 11.3 to 20.8), P = 0.024]. Results of multivariable Cox-regression analysis also identify that INHA anesthesia is significantly associated with mortality and cancer recurrence after surgery compare to TIVA, with HR (95%CI) of 1.303 (1.065, 1.595) and 1.265 (1.040, 1.539), respectively. Subgroup analysis suggested that in more severe cancer patients, the worse outcome related to INHA might be more significant. Conclusion This retrospective analysis identifies that TIVA is associated with better outcomes compared with INHA. Future prospective studies clinical and translational studies are required to verify this difference and investigate underlying pathophysiology.

NF-κB in the Vascular Progression of Melanoma

2004 ◽  
Vol 22 (4) ◽  
pp. 617-623 ◽  
Author(s):  
Mohammed Kashani-Sabet ◽  
Ladan Shaikh ◽  
James R. Miller ◽  
Mehdi Nosrati ◽  
Carlos M.M. Ferreira ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cox Regression ◽  
Surrogate Marker ◽  
Tissue Array ◽  
Matched Pair ◽  
Vascular Involvement ◽  
Tumor Vascularity ◽  
Data Set ◽  
Cox Regression Analysis ◽  
The Impact

Purpose To examine a model of melanoma progression based on vascular factors and the role of NF-κB in the vascular progression of melanoma. Patients and Methods A data set of 526 patients from the University of California San Francisco Melanoma Center with 2 years of follow-up or first relapse was studied. The impact of the presence or absence of various prognostic factors on overall survival of melanoma patients was assessed using Cox regression and Kaplan-Meier analysis. A matched-pair analysis of NF-κB expression was performed in cases with vascular involvement and increased tumor vascularity versus matched controls lacking these factors. Results Cox regression analysis of factors evaluated by the American Joint Committee on Cancer Melanoma Staging Committee reproduced the powerful impact of tumor thickness and ulceration in this data set. With the inclusion of vascular factors such as tumor vascularity and vascular involvement, ulceration was no longer significant in predicting overall survival. By multivariate analysis, vascular involvement and tumor vascularity were the strongest predictors of melanoma outcome. Tumor vascularity seems to be a precursor of both vascular involvement and ulceration. A matched-pair tissue array analysis demonstrated the significant correlation between overexpression of NF-κB–p65 and the development of vascular factors. Conclusion Vascular factors play an important role in the progression of malignant melanoma. Ulceration may be a surrogate marker for the interactions between melanoma and the tumor vasculature. NF-κB seems to play an important role in the development of these factors.

scholarly journals Ovarian Cancer Risk Scores Based on Immune-Related Pseudogenes to Predict Overall Survival and Guide Immunotherapy and Chemotherapy

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Jie Zhao ◽  
Rixiang Zhao ◽  
Xiaocen Wei ◽  
Xiaojing Jiang ◽  
Fan Su
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
High Risk ◽  
Cox Regression ◽  
High Risk Group ◽  
The Cancer Genome Atlas ◽  
Risk Scores ◽  
Ovarian Cancer Risk ◽  
Cox Regression Analysis ◽  
The Impact

Background. Ovarian cancer (OC) is the top of the aggressive malignancies in females with a poor survival rate. However, the roles of immune-related pseudogenes (irPseus) in the immune infiltration of OC and the impact on overall survival (OS) have not been adequately studied. Therefore, this study aims to identify a novel model constructed by irPseus to predict OS in OC and to determine its significance in immunotherapy and chemotherapy. Methods. In this study, with the use of The Cancer Genome Atlas (TCGA) combined with Genotype-Tissue Expression (GTEx), 55 differentially expressed irPseus (DEirPseus) were identified. Then, we constructed 10 irPseus pairs with the help of univariate, Lasso, and multivariate Cox regression analysis. The prognostic performance of the model was determined and measured by the Kaplan–Meier curve, a time-dependent receiver operating characteristic (ROC) curve. Results. After dividing OC subjects into high- and low-risk subgroups via the cut-off point, it was revealed that subjects in the high-risk group had a shorter OS. The multivariate Cox regression performed between the model and multiple clinicopathological variables revealed that the model could effectively and independently predict the prognosis of OC. The prognostic model characterized infiltration by various kinds of immune cells and demonstrated the immunotherapy response of subjects with cytotoxic lymphocyte antigen 4 (CTLA4), anti-programmed death-1 (PD-1), and anti-PD-ligand 1 (PD-L1) therapy. A high risk score was related to a higher inhibitory concentration (IC50) for etoposide ( P = 0.0099 ) and mitomycin C ( P = 0.0013 ). Conclusion. It was the first study to identify a novel signature developed by DEirPseus pairs and verify the role in predicting OS, immune infiltrates, immunotherapy, and chemosensitivity. The irPseus are vital factors predicting the prognosis of OC and could act as a novel potential treatment target.

scholarly journals Comparison of overall survival on surgical resection versus transarterial chemoembolization with or without radiofrequency ablation in intermediate stage hepatocellular carcinoma: A propensity score matching analysis

2020 ◽  
Author(s):  
Chih-Wen Lin ◽  
Yaw-Sen Chen ◽  
Gin-Ho Lo ◽  
Yao-Chun Hsu ◽  
Chia-Chang Hsu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Radiofrequency Ablation ◽  
Propensity Score ◽  
Propensity Score Matching ◽  
Surgical Resection ◽  
Cox Regression ◽  
Cox Regression Analysis ◽  
Tace Group ◽  
The Impact

Abstract Background: Patients with Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC) are recommended to undergo transcatheter arterial chemoembolization (TACE). However, TACE in combination with radiofrequency ablation (RFA) is not inferior to surgical resection (SR), and the benefits of surgical resection (SR) for BCLC stage B HCC remain unclear. Hence, this study aims to compare the impact of SR, TACE+RFA, and TACE on analyzing overall survival (OS) in BCLC stage B HCC. Methods: Overall, 428 HCC patients were included in BCLC stage B, and their clinical data and OS were recorded. OS was analyzed by the Kaplan-Meier method and Cox regression analysis. Results: One hundred forty (32.7%) patients received SR, 231 (53.9%) received TACE+RFA, and 57 (13.3%) received TACE. The OS was significantly higher in the SR group than that in the TACE+RFA group [hazard ratio (HR): 1.78; 95% confidence incidence (CI): 1.15-2.75, p=0.009]. The OS was significantly higher in the SR group than that in the TACE group (HR: 3.17; 95% CI: 2.31-4.36, p<0.0001). Moreover, the OS was significantly higher in the TACE+RFA group than that in the TACE group (HR: 1.82; 95% CI: 1.21-2.74, p=0.004). The cumulative OS rates at 1, 3 and 5 years in the SR, TACE+RFA, and TACE groups were 89.2%, 69.4% and 61.2%, 86.0%, 57.9% and 38.2%, and 69.5%, 37.0% and 15.2%, respectively. After propensity score matching, the SR group still had a higher OS than those of the TACE+RFA and TACE groups. The TACE+RFA group had a higher OS than that of the TACE group. Conclusion: The SR group had higher OS than the TACE+RFA and TACE groups in BCLC stage B HCC. Furthermore, the TACE+RFA group had higher OS than the TACE group.

scholarly journals Distant Survival for Patients Undergoing Surgery Using Volatile versus IV Anesthesia for Hepatocellular Carcinoma with Portal Vein Tumor Thrombus:A Retrospective study.

2020 ◽  
Author(s):  
Xiao-Yan Meng ◽  
Xiu-Ping Zhang ◽  
Hong-Qian Wang ◽  
Weifeng Yu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Portal Vein ◽  
Cox Regression ◽  
Cancer Recurrence ◽  
Survival Outcomes ◽  
Free Survival ◽  
Cox Regression Analysis ◽  
Underlying Causes ◽  
The Impact

Abstract Background Whether anesthesia type is associate with the surgical outcome of Hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) remains to be determined. This study aims to investigate the impact of volatile inhalational anesthesia (INHA) versus total IV anesthesia (TIVA) on the survival outcomes in HCC patients with PVTT. Methods A cohort of in-patients whom were diagnosed of HCC with PVTT in Eastern Hepatobiliary Surgery Hospital, Shanghai, China, from January 1, 2008 to December 24, 2012 were identified. Surgical patients receiving the INHA and TIVA were screened out. The overall survival (OS), recurrence-free survival (RFS) and several postoperative adverse events were compared according to anesthesia types. Results A total of 1513 patients were included in this study. After exclusions are applied, 263 patients remain in the INHA group and 208 in the TIVA group. Patients receiving INHA have a lower 5-year overall survival rate than that of patients receiving TIVA [12.6% (95% CI, 9.0 to 17.3) vs. 17.7% (95% CI, 11.3 to 20.8), P=0.024]. Results of multivariable Cox-regression analysis also identify that INHA anesthesia is significantly associated with mortality and cancer recurrence after surgery compare to TIVA, with HR (95%CI) of 1.303 (1.065, 1.595) and 1.265 (1.040, 1.539), respectively. Subgroup analysis suggested that in more severe cancer patients, the worse outcome related to INHA might be more significant. Conclusion This retrospective analysis identifies that TIVA has better survival outcomes compare to INHA in HCC patients with PVTT. Future prospective researches are urgent to verify this difference and figure out underlying causes of it.

Analysis of prognostic factors in patients with advanced relapsed/refractory NSCLC: Cox regression analysis of a randomized phase III trial comparing docetaxel and paclitaxel poliglumex (PPX)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7040-7040 ◽  
Author(s):  
P. Bonomi ◽  
C. Langer ◽  
M. O’Brien ◽  
K. O’Byrne ◽  
B. Bandstra ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cox Regression ◽  
Performance Status ◽  
Stage Iv ◽  
Tumor Stage ◽  
Phase Iii ◽  
Line Treatment ◽  
Phase Iii Trial ◽  
Cox Regression Analysis ◽  
The Impact

7040 Background: A phase III trial compared PPX to docetaxel as 2nd-line treatment in pts with relapsed/refractory advanced NSCLC (STELLAR 2). While overall survival was similar between arms, the need for supportive measures to manage the effects of myelosuppression was significantly reduced in the PPX arm. The current analysis was performed to evaluate determinants of survival in the 2nd-line treatment of NSCLC. Methods: STELLAR 2 enrolled 849 pts, 427 on PPX and 422 on docetaxel; all patients were included in the analysis. Randomization between the study arms was stratified by tumor stage, performance status (PS), start of frontline chemotherapy (< 4 mo vs more than 4 mo), gender, and prior taxane therapy. Univariate and multivariate Cox regression analyses were performed to evaluate the impact of baseline characteristics on overall survival (OS). Results: At randomization, 29% of pts had received prior taxane, 14% were PS2, 80% had stage IV disease, and 31% had started frontline therapy within the prior 4 months. Risk factors significantly affecting survival as determined by multivariate analysis are listed in the table . These factors were consistent when treatment was added to the model. Prior exposure to taxane was not predictive of survival; tumor stage was a significant univariate predictor (p=0.0349), but had relatively less impact in the multivariate model. Conclusion: These analyses identified several factors associated with reduced survival benefit from standard second line therapy. Consequently, alternative treatment strategies may be necessary in patients with poor prognosis. For example, more tolerable agents may enhance the benefit/toxicity ratio in these patients. [Table: see text] [Table: see text]

Correlation of high density of CD8+and FoxP3+ lymphocytes with overall survival in intestinal-type periampullary adenocarcinoma.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 266-266
Author(s):  
Carl Fredrik Warfvinge ◽  
Jacob Elebro ◽  
Margareta Heby ◽  
Bjorn Nodin ◽  
Jakob Eberhard ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cox Regression ◽  
Multivariable Analysis ◽  
High Density ◽  
Intestinal Type ◽  
Periampullary Cancer ◽  
Type I ◽  
Cox Regression Analysis ◽  
Periampullary Adenocarcinoma ◽  
The Impact

266 Background: Periampullary cancers can be divided into different morphological subtypes where those having an intestinal-type (I-type) morphology have a better prognosis than those with a pancreatobiliary-type (PB-type) morphology. In recent years much focus of antineoplastic research has been directed towards the central role played by various subsets of T-lymphocytes. Yet, very little is known of their role in different subtypes of periampullary cancer. Therefore, the aim of this study was to analyze the density of CD8+ (cytotoxic) and FoxP3+ (regulatory) T-cells in periampullary cancer, with particular reference to their relationship with survival by morphological subtype. Methods: Immunohistochemical expression of CD8 and FoxP3-positive tumor-infiltrating lymphocytes (TILs) was analyzed in tissue microarrays with tumors from 175 consecutive cases of periampullary adenocarcinoma, 110 of PB-type and 65 of I-type morphology, treated with pancreaticoduodenectomy. Kaplan-Meier and univariable and multivariable Cox regression analysis, adjusted for age, T-stage, N-stage, grade, sex, invasion of blood vessels, lymphatic vessels, adjuvant chemotherapy and resection margins were applied to determine the impact of CD8 and FoxP3 expression on 5-year overall survival (OS). Results: In I-type tumors, a high density of CD8+ as well as FoxP3+ TILs was significantly associated with a prolonged overall survival (HR = 0.39, 95% CI 0.19-0.80 and HR = 0.32, 95% CI 0.15 –0.67). The association between high density of FoxP3+ TILs and survival remained significant in multivariable analysis (HR = 0.37, 95% CI 0.17-0.84) while the association between CD8+ TILs and survival did not. The density of CD8+ and FoxP3+ TILs was not prognostic in PB-type tumors. Conclusions: High density of CD8+ and FoxP3+ TILs correlates with a prolonged overall survival in I-type but not in PB-type periampullary adenocarcinomas. Thus, morphological subtype appears to be an important determinant of the prognostic and predictive impact of the inflammatory microenvironment in periampullary carcinoma, and should be considered in future studies.

The impact of PBRM1 mutations on overall survival in greater than 2,100 patients treated with immune checkpoint blockade (ICB).

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 666-666 ◽  
Author(s):  
A. Ari Hakimi ◽  
Yasser Ged ◽  
Jessica Flynn ◽  
Douglas R Hoen ◽  
Renzo G Di Natale ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Second Line ◽  
Loss Of Function ◽  
First Line ◽  
Vegf Inhibitors ◽  
Cell Renal Cell Carcinoma ◽  
Cox Regression Analysis ◽  
The Impact

666 Background: PBRM1 is the second most commonly mutated gene in clear cell renal cell carcinoma (ccRCC). We have previously shown favorable outcomes in PBRM1-mutated ccRCC tumors treated with vascular endothelial growth factor (VEGF) inhibitors. Recent data suggested PBRM1 mutations may sensitize ccRCC and non RCC malignancies to ICB therapy. We queried the impact of PBRM1 loss on overall survival (OS) across 2,152 patients treated with ICB. Methods: PBRM1 mutations were assessed in metastatic ccRCC patients who received first line (n = 82) or second line (n = 61) ICB or ICB/VEGF combinations. Additionally, 41 cohorts of non-RCC malignancies treated with ICB and combination (n = 2,009) were analyzed. Mutations were assessed by next generation targeted sequencing using archival tissue. Association of mutation status and overall survival (OS) was tested by multivariate Cox regression analysis (MVA) and adjusted for tumor mutation burden (TMB), copy number alterations (CNA), loss of function(LOF) mutations (non RCC cohort) and IMDC risk (for ccRCC patients). Results: PBRM1 mutations were not associated with improved OS in ICB the entire ccRCC cohort (HR 1.37; CI 0.79-2.4; p = 0.265), the first line (p = 0.624) or second line setting (p = 0.39) or as combination with VEGF inhibitors (p = 0.2). Several RCC subgroups were investigated (see Table at bottom). In the non-RCC cohorts (n = 2,009) PBRM1 mutations were not significantly associated with OS on univariate analysis (HR = 0.73, p = 0.22 for LOF and HR = 0.84,p = 0.34 for non LOF), and remained insignificant after adjusting for TMB, total CNA, and drug class (CTLA4, PD-1/PDL-1 and combinations) (HR = 1.07, p = 0.78 for LOF and HR = 1.08,p = 0.67 for non LOF). Conclusions: Neither in ccRCC nor in the pan-cancer cohort did PBRM1 mutations appear to be associated with improved overall survival with ICB therapy.[Table: see text]

Cisplatin-Based versus Carboplatin-Based Chemotherapy for Extra-Pulmonary Neuroendocrine Carcinomas; A Real-World Study.

2021 ◽  
Author(s):  
Omar Abdel-Rahman ◽  
Sheryl L. Koski
Keyword(s):  
Overall Survival ◽  
Regression Analysis ◽  
Cox Regression ◽  
Survival Outcomes ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Platinum Agent ◽  
Extra Pulmonary ◽  
The Impact ◽  
Neuroendocrine Carcinomas

Objective: To assess the survival differences between cisplatin/etoposide versus carboplatin/etoposide chemotherapy regimens in the management of extra-pulmonary neuroendocrine carcinomas (NECs). Methods: Administrative cancer care databases in the province of Alberta, Canada were reviewed, and patients with extra-pulmonary NECs (including those with small cell and large cell neuroendocrine carcinomas) who were treated with either cisplatin/ etoposide or carboplatin/ etoposide, 2004-2019, were reviewed. Kaplan-Meier survival estimates were used to compare the survival outcomes according to the type of platinum agent, and multivariable Cox regression analysis was used to assess the impact of the type of platinum agent on overall survival outcomes. Results: A total of 263 eligible patients were included in this analysis. These include 176 patients who received cisplatin/ etoposide and 87 patients who received carboplatin/etoposide. Using Kaplan-Meier survival estimates, patients treated with cisplatin have better overall survival compared to patients treated with carboplatin (P=0.005). Multivariable Cox regression analysis suggested that the following factors were associated with worse overall survival: higher Charlson comorbidity index (HR: 1.17; 95% CI: 1.05-1.30), gastrointestinal primary site (HR: 1.55; 95% CI: 1.12-2.14), stage IV disease (HR: 1.75; 95% CI: 1.28-2.38) and use of carboplatin (HR: 1.40; 95% CI: 1.02-1.92). Conclusions: The current study suggested that cisplatin/etoposide might be associated with better overall survival compared to carboplatin/etoposide among patients with extra-pulmonary NECs. It is unclear if this is related to differences in inherent responsiveness to the two platinum agents, or due to differences in comorbidity burden between the two treatment groups.

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