scholarly journals Positive Programmed Cell Death-Ligand 1 Expression Predicts Poor Treatment Outcomes in Esophageal Squamous Cell Carcinoma Patients Receiving Neoadjuvant Chemoradiotherapy

2019 ◽  
Vol 8 (11) ◽  
pp. 1864 ◽  
Author(s):  
Huang ◽  
Lu ◽  
Wang ◽  
Chen ◽  
Lo ◽  
...  

Background: Programmed cell death-ligand 1 (PD-L1) is present in a subgroup of cancer patients who may be favorable targets for immune checkpoint inhibitor therapies. However, the significance of the PD-L1 expression in esophageal squamous cell carcinoma (ESCC) patients receiving neoadjuvant chemoradiotherapy remains unclear. Methods: By means of PD-L1 immunohistochemistry 22C3 pharmDx assay, we evaluate the PD-L1 expression and its association with clinical outcome in 107 ESCC patients receiving neoadjuvant chemoradiotherapy. Results: Patients with positive PD-L1 expression have significantly lower pathological complete response rates (13% versus 32%; P = 0.036) than those with negative PD-L1 expression. Univariate survival analysis found that positive PD-L1 expression were correlated with poor overall survival (P = 0.004) and inferior disease-free survival (P < 0.001). In a multivariate analysis, positive PD-L1 expression was independently associated with the absence of a pathologically complete response (P = 0.044, hazard ratio: 3.542), worse overall survival (P = 0.006, hazard ratio: 2.017), and inferior disease-free survival (P < 0.001, hazard ratio: 2.516). Conclusions: For patients with ESCC receiving neoadjuvant chemoradiotherapy, positive PD-L1 expression independently predicts the poor chemoradiotherapy response and worse treatment outcome. Thus, our data suggests that PD-L1 may be an influential biomarker for prognostic classification and for immune checkpoint inhibitor therapies in ESCC patients receiving neoadjuvant chemoradiotherapy.

Author(s):  
Iuri Pedreira Fillardi ALVES ◽  
Valdir TERCIOTI JUNIOR ◽  
João de Souza COELHO NETO ◽  
José Antonio Possatto FERRER ◽  
José Barreto Campello CARVALHEIRA ◽  
...  

ABSTRACT Background Multimodal therapy with neoadjuvant chemoradiotherapy, followed by esophagectomy has offered better survival results, compared to isolated esophagectomy, in advanced esophageal cancer. In addition, patients who have a complete pathological response to neoadjuvant treatment presented greater overall survival and longer disease-free survival compared to those with incomplete response. Aim: To compare the results of overall survival and disease-free survival among patients with complete and incomplete response, submitted to neoadjuvant chemoradiotherapy, with two therapeutic regimens, followed by transhiatal esophagectomy. Methods: Retrospective study, approved by the Research Ethics Committee, analyzing the medical records of 56 patients with squamous cell carcinoma of the esophagus, divided into two groups, submitted to radiotherapy (5040 cGY) and chemotherapy (5-Fluorouracil + Cisplatin versus Paclitaxel + Carboplatin) neoadjuvants and subsequently to surgical treatment, in the period from 2005 to 2012, patients. Results The groups did not differ significantly in terms of gender, race, age, postoperative complications, disease-free survival and overall survival. The 5-year survival rate of patients with incomplete and complete response was 18.92% and 42.10%, respectively (p> 0.05). However, patients who received Paclitaxel + Carboplatin, had better complete pathological responses to neoadjuvant, compared to 5-Fluorouracil + Cisplatin (47.37% versus 21.62% - p = 0.0473, p <0.05). Conclusions There was no statistical difference in overall survival and disease-free survival for patients who had a complete pathological response to neoadjuvant. Patients submitted to the therapeutic regimen with Paclitaxel and Carboplastin, showed a significant difference with better complete pathological response and disease progression. New parameters are indicated to clarify the real value in survival, from the complete pathological response to neoadjuvant, in esophageal cancer.


2018 ◽  
Vol 97 (7) ◽  
pp. 759-766 ◽  
Author(s):  
G. Troiano ◽  
F. Mastrangelo ◽  
V.C.A. Caponio ◽  
L. Laino ◽  
N. Cirillo ◽  
...  

Oral squamous cell carcinoma (OSCC) is a common type of cancer characterized by a low survival rate, mostly due to local recurrence and metastasis. In view of the importance of predicting tumor behavior in the choice of treatment strategies for OSCC, several studies have attempted to investigate the prognostic value of tissue biomarkers, including microRNA (miRNA). The purpose of this study was to perform a systematic review and meta-analysis to evaluate the relationship between miRNA expression and survival of OSCC patients. Studies were identified by searching on MEDLINE/PubMed, SCOPUS, Web of Science, and Google Scholar. Quality assessment of studies was performed with the Newcastle-Ottawa Scale. Data were collected from cohort studies comparing disease-free survival and overall survival in patients with high miRNA expression compared to those with low expression. A total of 15 studies featuring 1,200 OSCC samples, predominantly from Asia, met the inclusion criteria and were included in the meta-analysis. Poor prognosis correlated with upregulation of 9 miRNAs (miR-21, miR-455-5p, miiR-155-5p, miR-372, miR-373, miR-29b, miR-1246, miR-196a, and miR-181) and downregulation of 7 miRNAs (miR-204, miR-101, miR-32, miR-20a, miR-16, miR-17, and miR-125b). The pooled hazard ratio values (95% confidence interval) related to different miRNA expression for overall survival and disease-free survival were 2.65 (2.07–3.39) and 1.95 (1.28–2.98), respectively. The results of this meta-analysis revealed that the expression levels of specific miRNAs can robustly predict prognosis of OSCC patients.


2019 ◽  
Vol 47 (5) ◽  
pp. 1829-1842 ◽  
Author(s):  
Weimin Xu ◽  
Yilian Zhu ◽  
Wei Shen ◽  
Wenjun Ding ◽  
Tingyu Wu ◽  
...  

Objective Prognostic prediction of colorectal cancer (CRC) remains challenging because of its heterogeneity. Aberrant expression of caudal-type homeobox transcription factor 2 (CDX2) is strongly correlated with the prognosis of CRC. Methods Tissue samples of patients with CRC who underwent surgery in Xinhua Hospital (Shanghai, China) from January 2010 to January 2013 were collected. CDX2 expression was semiquantitatively evaluated via immunohistochemistry. Results In total, 138 patients were enrolled in this study from a prospectively maintained institutional cancer database. The median follow-up duration was 57.5 months (interquartile range, 17.0–71.0 months). In the Cox proportional hazards model, low CDX2 expression combined with stage T4 CRC was significantly the worst prognostic factor for disease-free survival (hazard ratio = 7.020, 95% confidence interval = 3.922–12.564) and overall survival (hazard ratio = 5.176, 95% CI = 3.237–10.091). In the Kaplan–Meier survival analysis, patients with low CDX2 expression and stage T4 CRC showed significantly worse disease-free survival and overall survival than those with low CDX2 expression alone. Conclusion CDX2 expression combined with the T stage was more accurate for predicting the prognosis of CRC. Determining the prognosis of CRC using more than one variable is valuable in developing appropriate treatment and follow-up strategies.


1986 ◽  
Vol 4 (6) ◽  
pp. 838-846 ◽  
Author(s):  
V Vinciguerra ◽  
K J Propert ◽  
M Coleman ◽  
J R Anderson ◽  
L Stutzman ◽  
...  

A randomized clinical trial of combination chemotherapy for patients who relapsed following primary radiation therapy for Hodgkin's disease was conducted from 1975 to 1981 by the Cancer and Leukemia Group B (CALGB). One hundred thirteen patients were prospectively randomized to receive 12 cycles of either CVPP (CCNU, vinblastine, procarbazine, and prednisone), ABOS (bleomycin, vincristine [Oncovin; Lilly, Indianapolis], doxorubicin [Adriamycin, Adria Laboratories, Columbus, Ohio], and streptozotocin), or alternating cycles of CVPP and ABOS. The median length of observation for patients in this report is 4 years. Toxicities of the three treatment programs were primarily hematologic. Frequencies of complete response were 72% for CVPP, 70% for ABOS, and 82% for CVPP/ABOS (P = .37). Females and patients who had nodular sclerosing disease at initial diagnosis had significantly higher complete response rates. The 5-year disease-free survival for the complete responders was 55%; the 5-year overall survival was 60%. There were no significant differences among the treatments on disease-free survival (P = .78) or overall survival (P = .18). Age under 40 years was the only significant positive prognostic factor for disease-free survival (P = .095) and overall survival (P = .003). This study demonstrates no statistically significant advantage for alternating cycles of combination chemotherapy in affecting complete response frequency, disease-free survival, or overall survival as compared with therapy with CVPP or ABOS alone. However, the power to detect differences in these outcome parameters is somewhat limited by the sample sizes.(ABSTRACT TRUNCATED AT 250 WORDS)


2018 ◽  
Vol 31 (Supplement_1) ◽  
pp. 153-153
Author(s):  
Oliver Koch ◽  
Andreas Tschoner ◽  
Richard Partl ◽  
Alexander Perathoner ◽  
Philipp Gehwolf ◽  
...  

Abstract Background The aim of this study is to compare the outcome of patients with adenocarcinoma of the distal oesophagus (AEG Type I) treated with perioperative chemotherapy or neoadjuvant chemoradiation. Methods A retrospective analysis of eligible patients from four Austrian centers was conducted. All patients with AEG type I treated between January 2007 and October 2017 with chemotherapy (EOX-protocol) or chemoradiation (CROSS-protocol, or 5-FU/Cisplatin), followed by oesophagectomy were included in the study. Primary outcomes overall survival, and disease free survival as well as secondary outcomes, achievement of pathological complete response pCR (ypT0N0M0) or downstaging of T- or N-stage were analyzed. Primary outcomes were calculated by the Kaplan-Meier-method. Results Data of 117 patients were analyzed, 59 received chemoradiation (50/59 CROSS and 9/59 5-FU/Cisplatin) and 58 patients received perioperative chemotherapy (EOX). Complete data at time of submission were available in 40 patients in the chemoradiation group and in 37 patients in the chemotherapy group. The median follow-up time in the chemoradiation group was 13,0 months (CI 95%: 11,0–15,0) and in the chemotherapy group 45,0 months (CI 95%: 28,8–61,3). Overall survival rate in the EOX group after ½, 1, 3 and 5 years was 92%, 83%, 63% and 34%. So far long term data are not available after chemoradiation, after ½ year overall survival was 84% and after one year 60%. Disease free survival rate in the EOX group after ½, 1, 3 and 5 years was 91%, 81%, 54% and 32%, in the chemoradiation group after ½ and one year 80% and 50%. A significant difference was found in the pathological complete response (pCR) rate, it was achieved in 19% of patients after chemoradiation and in 3% after chemotherapy (P = 0000). Conclusion Concerning major response of the primary tumor there are clear advantages for chemoradiation. In regards to systemic tumor control there seems a tendency in favor for chemotherapy. Disclosure All authors have declared no conflicts of interest.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5473-5473
Author(s):  
Naibai Chang ◽  
Xichun Gu ◽  
Ling Zhu ◽  
Jianping Wei ◽  
Shengming Zhao ◽  
...  

Abstract Objective: Anthracycline-based chemotherapy induces 50%–70% of CR in patients with lymphoma, but only 30%–40% of long-term disease-free survival. Salvage chemotherapy with autologous stem cell rescue is required in patients with aggressive disease or never achieve CR with conventional chemotherapy,but the relapsed rate is still high. The purpose of this study was to evaluate radiotherapy post autologous stem cell transplantation in such group of patients. Methods: 15 patients who underwent autologous stem cell transplantation during 1992–1998 were enrolled in this study. Conditioning regimen was CBV (cyclophosphomide + carmustine + etoposide). Radiotherapy was started on day +50(31–90). All patients were followed up until January 2005. Kaplan-Mier survival analysis was made by using SPSS10.0 software. Results: There were 14 patients with non-Hodgkin lymphoma and 1 with Hodgkin disease enrolled. Male:female=11:4. Median age was 40 (30–64). At least 6 cycles of induction chemotherapy were given before transplantation. There were 3 patients in progression disease, 1 in stable disease, and 11 in partial remission before transplantation. Three patients received total lymph node irradiation (TLI). Seven patients received TBI(200cGY)+involved field irradiation therapy(IFIT). Five were treated with IFIT. All patients acheaved complete response(including 1 CRu) after radiotherapy. Three patients relapsed. One patient treated with TBI+IFIT relapsed at 6 months later. Two patients treated with IFIT relapsed at 8 and 36 months later respectively. The mean disease-free survival and overall survival were 10.84(SD1.37,95%CI) years and 11.89(SD1.35,95%CI) years respectively. The estimatrd 10-year disease-free survival and Overall survival were both 73%. One patient developed AML at 86 month. Grade III–IV hematologic toxicity was seen in 2 patients. Conclusions: Post ASCT radiotherapy is safe and tolerated. Relaps rate is low. Patients who received TLI or TBI+IFIT seem to have better outcome than that received IFIT only.


2019 ◽  
Vol 111 (9) ◽  
pp. 887-902 ◽  
Author(s):  
Felix J Hüttner ◽  
Pascal Probst ◽  
Eva Kalkum ◽  
Matthes Hackbusch ◽  
Katrin Jensen ◽  
...  

Abstract Background Current guidelines recommend neoadjuvant therapy for patients with stage II or III rectal cancer. The addition of platinum derivatives to fluoropyrimidine-based chemoradiotherapy has been frequently investigated, but their role in this setting remains controversial. Methods PubMed, Cochrane Library, and Web of Science were systematically searched for randomized trials comparing chemoradiotherapy with or without platinum agents in stage II or III rectal cancer. Main outcome parameters were overall and disease-free survival, additional outcomes included pathological complete response, isolated local recurrence, distant recurrence, toxicity, and perioperative morbidity. Time-to-event data were pooled as hazard ratios (HRs) by the inverse variance method and binary outcomes as odds ratios (ORs) by the Peto method with their respective 95% confidence interval (CI). All statistical tests were two-sided. Results Ten randomized controlled trials with data on 5599 patients were included in the meta-analysis. Platinum derivatives did not statistically significantly improve overall survival (HR = 0.93, 95% CI = 0.82 to 1.05, P = .23), disease-free survival (HR = 0.91, 95% CI = 0.83 to 1.01, P = .07), or local recurrence (OR = 0.83, 95% CI = 0.66 to 1.05, P = .12). However, it led to a statistically significant increase of pathological complete response (OR = 1.31, 95% CI = 1.10 to 1.55, P = .002) and a statistically significant reduction of distant recurrence (OR = 0.78, 95% CI = 0.66 to 0.92, P = .004). Benefits were accompanied by higher rates of grade 3 or 4 toxicities. Conclusions Intensified neoadjuvant chemoradiotherapy with the addition of platinum derivatives cannot be recommended routinely because it did not improve overall or disease-free survival and was associated with increased toxicity. It needs to be elucidated whether the benefits in distant recurrence and pathological complete response may be advantageous for selected high-risk patients.


2020 ◽  
Vol 16 (10) ◽  
pp. 559-571
Author(s):  
Shichao Zhou ◽  
Haihua Yuan ◽  
Jiongyi Wang ◽  
Xiaohua Hu ◽  
Feng Liu ◽  
...  

Aim: To explore the prognostic value of the systemic inflammatory marker (SIM) based on neutrophil, lymphocyte and monocyte counts in head and neck squamous cell carcinoma (HNSCC) patients. Patients & methods: We retrospectively collected the data of 367 patients with HNSCC who underwent surgery. The Kaplan–Meier survival analysis and Cox regression analysis were conducted on disease-free survival and overall survival. Results: A high SIM (>1.34) was associated with larger tumor size, advanced clinical stage and shorter survival time. The survival analysis showed that only clinical stage and SIM were independent prognostic indicators of disease-free survival and overall survival. Conclusion: The SIM positively correlated with tumor progression and might be a powerful prognostic indicator of poor outcome in patients with HNSCC.


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