p53 adapted neoadjuvant therapy for esophageal cancer: Pilot study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4535-4535 ◽  
Author(s):  
D. Kandioler ◽  
M. Hejna ◽  
R. Zwrtek ◽  
S. Kappel ◽  
C. Bichler ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Neoadjuvant Therapy ◽  
Squamous Cell ◽  
Direct Sequencing ◽  
P53 Gene ◽  
P53 Mutation ◽  
Chemotherapy Response ◽  
Surgical Specimen ◽  
Overall Response

4535 Background: Randomized trials could not yet prove clinical efficacy of neoadjuvant chemotherapy for esophageal cancer. A survival benefit could be shown for treatment responders only. Using platinum based regimen, yet about 20 % of patients can achieve pathological complete remission which translates in reported 3-year survival rates of 64% in this group. Factors identifying this subgroup of responders and selecting optimal drugs for non responders could dramatically enhance treatment efficacy. Several studies suggest that mutations in the p53 gene may induce drug resistance especially for agents whose effect is based on apoptosis induction, like Cisplatin. Methods: In order to test the hypothesis that the p53 genotype is predictive for chemotherapy response, a prospective study was conducted. Thirty-eight patients with potentially respectable esophageal cancer were evaluated for the relation between p53 genotype and response to two different neoadjuvant treatments. P53 gene mutations were assessed by complete direct sequencing of DNA extracted from diagnostic biopsies. Response to neoadjuvant chemotherapy was assessed pathohistologically in the surgical specimen. Results: 20 squamous cell carcinoma and 18 adenocarcinoma were included. Overall the p53 mutation rate was 58% (22/38), with 66 % for squamous cell and 53% for adenocarcinomas, respectively. 30 patients received CIS/5FU (cisplatin 80mg/m2 d1 5-FU 1,000mg/m2 d 1–5, q21,2 cycles), 8 received docetaxel (75mg/m2, q21,2 cycles). The overall response rate was 48% (18/38). Patients with p53 mutation did not respond to CIS/5-FU (0/16), while all mutant patients responded to docetaxel (6/6). The overall response to p53 adapted neoadjuvant therapy was 94%. P53 adapted treatment was associated with a significant survival advantage (p=0,042) after a median follow up of 15,4 months. Conclusions: A prospective randomized trial was initiated to test the interaction between the predictive marker p53 and response to CIS/5-FU and Docetaxel, respectively. [Table: see text] No significant financial relationships to disclose.

Squamous cell carcinoma antigen: prognostic significance and role in the monitoring of neoadjuvant chemotherapy response in cervical cancer.

1994 ◽  
Vol 12 (11) ◽  
pp. 2309-2316 ◽  
Author(s):  
G Scambia ◽  
P Benedetti Panici ◽  
E Foti ◽  
M Amoroso ◽  
G Salerno ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Squamous Cell Carcinoma ◽  
Neoadjuvant Chemotherapy ◽  
Squamous Cell ◽  
Locally Advanced ◽  
Chemotherapy Response ◽  
Advanced Cervical Cancer ◽  
Squamous Cell Carcinoma Antigen ◽  
Locally Advanced Cervical Cancer ◽  
Response To Neoadjuvant Chemotherapy

PURPOSE The aim of the study was to investigate the role of squamous cell carcinoma antigen (SCC) in the management of patients with locally advanced cervical cancer treated by neoadjuvant chemotherapy and radical surgery. PATIENTS AND METHODS SCC assay was performed with a radioimmunoassay kit in a series of 102 patients with locally advanced cervical cancer. The values of 2.5, 5, and 7 ng/mL were used to define SCC antigen positivity. The chi 2 and Fisher's exact test and the stepwise logistic regression were used to evaluate the distribution of marker values. Analysis of survival was performed using the Kaplan and Meier test and Cox multivariate regression analysis. RESULTS SCC levels were elevated in 65%, 45%, and 32% of patients with primary tumors for cutoff values of 2.5, 5, and 7 ng/mL, respectively. SCC pretreatment levels correlated with stage, tumor volume and lymph node status. In the multivariate analysis, SCC expression proved to be an independent predictor of response to neoadjuvant chemotherapy. SCC posttreatment levels were strongly related to chemotherapy response. Moreover, the overall correlation between the clinical course of the disease and the variation of SCC levels was 83%. In patients with squamous cell tumors, survival was significantly longer in SCC-negative cases compared with SCC-positive cases (P = .04). Moreover, in patients undergoing surgery after response to neoadjuvant chemotherapy, low SCC values were associated with better prognosis (P = .02). In the multivariate analysis, parametrial involvement and SCC status proved to retain an independent prognostic value. CONCLUSION Our data show that SCC assay may provide useful information to improve the prognostic characterization and disease monitoring of patients with locally advanced cervical cancer undergoing neoadjuvant chemotherapy.

scholarly journals Serum IgG Level Is A Predicting Factor for the Response to Neoadjuvant Chemotherapy In Patients With Esophageal Squamous Cell Carcinoma

2021 ◽  
Author(s):  
Seiichi Nakaya ◽  
Ryo Ogawa ◽  
Shunsuke Hayakawa ◽  
Shiro Fujihata ◽  
Tomotaka Okubo ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Squamous Cell ◽  
Cell Cancer ◽  
Chemotherapy Response ◽  
Serum Igg ◽  
Response To Chemotherapy ◽  
Response Group ◽  
Serum Igg Levels ◽  
Igg Level ◽  
Pretreatment Serum

Abstract BackgroundDespite the established oncological benefits of neoadjuvant chemotherapy for esophageal squamous cell cancer, not all cases demonstrate benefit. Hence, predicting the response to chemotherapy before treatment is desirable. Some reports have shown that immune factors are related to the chemotherapy response. This study aimed to investigate the utility of serum IgG levels for predicting chemotherapy response.MethodsResponse to chemotherapy and pretreatment serum IgG levels were examined in 77 cases who underwent esophagectomy after neoadjuvant chemotherapy for esophageal squamous cell cancer.ResultsThe effective response group had significantly lower serum IgG levels than the ineffective response group (p < 0.001). Univariate and multivariate analyses revealed serum IgG level to be an independent predictor for response to chemotherapy (p = 0.001). Furthermore, cases with effective pathological response had significantly lower pretreatment serum IgG levels than those who did not (p = 0.006).ConclusionsOur finding showed that serum IgG levels can be a predictor of the response to neoadjuvant chemotherapy for esophageal squamous cell carcinoma.Trial registrationThis retrospective study was approved by the review board of Nagoya City University Graduate School of Medical Sciences (reception number: 60-18-0008).

Nuclear SMAD4 as a predictor of survival in patientes with extremity soft tissue sarcomas submitted to neoadjuvant chemotherapy.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 10586-10586
Author(s):  
Isabela Werneck Cunha ◽  
Ranyell Spencer Sobreira Batista ◽  
Paulo Roberto Stevanato ◽  
Samuel Aguiar ◽  
Ademar Lopes ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Neoadjuvant Chemotherapy ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Soft Tissue Sarcomas ◽  
Disease Free Survival ◽  
Chemotherapy Response ◽  
Surgical Specimen ◽  
Viable Cells ◽  
Low Expression

10586 Background: Neoadjuvant chemotherapy for locally advanced soft tissue sarcomas, although not standard, represents a promising option for resectable tumours. The discovery of biological predictors of chemotherapy response highlights the possibility to develop individualised therapeutic approaches in selected group of patients or predict survival also. The SMAD4 protein, a member of TGFβ superfamily has a role in progression and tumor metastasis and may be involved sarcomas recurrence. Methods: 30 patients with soft tissue sarcomas (STS) of high-grade located in extremities treated with neoadjuvant doxorubicin and ifosfamide chemotherapy were observed prospectively since January 2005 to June 2011. All patients were submitted to radiation therapy adjuvant. Surgical specimens after neoadjuvant treatment were evaluated of SMAD4 nuclear expression by immuno-histochemistry and percentage of viable cells Results: The median follow-up time was 42 months. The overall survival (OS) was 91.7% in patients with low expression SMAD4 nuclear protein associated with ≤10% of viable cells (n=12) in the surgical specimen and 68.9% in the remaining patients. Likewise, the disease free survival (DSF) was 91.7% versus 38.6% (p 0.01) respectively. Conclusions: The combination of nuclear SMAD4 low expression and 10% or less of viable cells in the surgical specimen was statistically significant in better DFS in patients with locally advanced extremity STS treated with neoajuvant chemotherapy with benefit in OS.

scholarly journals Esophageal Cancer: Neoadjuvant therapy for squamous cell esophageal carcinoma

1994 ◽  
Vol 5 ◽  
pp. S17-S26 ◽  
Author(s):  
U. Fink ◽  
H.J. Stein ◽  
H. Bochtler ◽  
J.D. Roder ◽  
H.J. Wilke ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Esophageal Carcinoma ◽  
Neoadjuvant Therapy ◽  
Squamous Cell

Changes in modified Glasgow prognostic score after neoadjuvant chemotherapy is a prognostic factor in clinical stage II/III esophageal cancer

2016 ◽  
Vol 29 (2) ◽  
pp. 146-151 ◽  
Author(s):  
Yasunori Otowa ◽  
Tetsu Nakamura ◽  
Gosuke Takiguchi ◽  
Ayako Tomono ◽  
Masashi Yamamoto ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Prognostic Factor ◽  
Neoadjuvant Chemotherapy ◽  
Squamous Cell ◽  
Prognostic Score ◽  
Clinical Stage ◽  
Glasgow Prognostic Score ◽  
Serum Levels ◽  
Stage Ii ◽  
Modified Glasgow Prognostic Score

Summary The inflammation-based modified Glasgow prognostic score (mGPS) has been shown to be a prognostic factor for esophageal cancer, but its changes in relation to neoadjuvant chemotherapy (NAC) have never been discussed. The purpose of this study was to evaluate the potential prognostic role of mGPS with regard to NAC. mGPS was evaluated on the basis of admission blood samples taken before chemotherapy and before surgery. Patients with elevated C-reactive protein (CRP) serum levels (&gt;10 mg/L) and hypoalbuminemia (&lt;35 g/L) were allocated a score of 2, patients with elevated CRP serum levels without hypoalbuminemia were allocated a score of 1, and patients with normal CRP serum levels with or without hypoalbuminemia were allocated a score of 0. A total of 100 patients with clinical stage II/III squamous cell esophageal cancer, who underwent NAC and esophagectomy between January 2007 and August 2012, were investigated. From the multivariate analysis, the grade of response to chemotherapy and post-NAC mGPS level was found to be independent prognostic factors. The overall survival rate was significantly higher in the conserved mGPS group than in the worse mGPS group (P = 0.030). Changes in mGPS during chemotherapy affected the prognosis of patients, and post-NAC mGPS is an independent prognostic factor in patients with clinical stage II/III thoracic esophageal squamous cell cancer.

scholarly journals Serum IgG level is a predicting factor for the response to neoadjuvant chemotherapy in patients with esophageal squamous cell carcinoma

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Seiichi Nakaya ◽  
Ryo Ogawa ◽  
Shunsuke Hayakawa ◽  
Shiro Fujihata ◽  
Tomotaka Okubo ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Squamous Cell ◽  
Chemotherapy Response ◽  
Effective Response ◽  
Serum Igg ◽  
Response To Chemotherapy ◽  
Response Group ◽  
Serum Igg Levels ◽  
Igg Level ◽  
Pretreatment Serum

Abstract Background Despite the established oncological benefits of neoadjuvant chemotherapy for esophageal squamous cell cancer, not all cases demonstrate benefit. Hence, predicting the response to chemotherapy before treatment is desirable. Some reports have shown that immune factors are related to the chemotherapy response. This study aimed to investigate the utility of serum IgG levels for predicting chemotherapy response. Methods Among the patients who underwent esophagectomy after neoadjuvant chemotherapy at Nagoya City University Hospital between December 2012 and June 2019, 130 cases were included in this study. Response to chemotherapy and pretreatment serum IgG levels were examined in 77 cases. FP (5-fluorouracil and cisplatin) therapy or DCF (docetaxel, cisplatin, and 5-FU) therapy was performed as neoadjuvant chemotherapy. DCF therapy was selected for patients aged <75 years, who could be safely administered chemotherapy based on their medical history. Results This study divided cases into two groups: the effective response group (PR) and ineffective response group (SD and PD). We classified 1, 37, and 39 cases as PD, PR, and SD, respectively. None of the cases were classified as CR. The effective response group had significantly lower serum IgG levels than the ineffective response group (p < 0.001). The cutoff serum IgG value was determined to be 1087 mg/dL. The low IgG group had significantly more cases who had effective response to chemotherapy compared with the high IgG group (odds ratio [OR] = 9.009; 95% confidence interval [CI] = 2.974–30.157; p < 0.001). Univariate and multivariate analyses revealed serum IgG level to be an independent predictor for response to chemotherapy (p = 0.001). Furthermore, cases with effective pathological response had significantly lower pretreatment serum IgG levels than those who did not (p = 0.006). Conclusions Our finding showed that serum IgG levels can be an independent predictor of the response to neoadjuvant chemotherapy for esophageal squamous cell carcinoma. Trial registration This retrospective study was approved by the review board of Nagoya City University Graduate School of Medical Sciences (reception number: 60-18-0008).

444 CORRELATION BETWEEN PATHOLOGIC COMPLETE RESPONSE TO NEOADJUVANT THERAPY AND RECURRENCE IN PATIENTS WITH ESOPHAGEAL CANCER

2021 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Durgatosh Pandey ◽  
Rambha Pandey ◽  
Pramod Kumar Julka
Keyword(s):  
Esophageal Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Neoadjuvant Therapy ◽  
Pathologic Complete Response ◽  
Neoadjuvant Chemoradiotherapy ◽  
Postoperative Mortality ◽  
Effective Treatment Option ◽  
Relative Significance ◽  
Carcinoma Esophagus ◽  
Pathological Cr

Abstract   Multimodal treatment options in carcinoma esophagus include neoadjuvant chemoradiotherapy or chemotherapy followed by surgery. The degree of pathologic response to different neoadjuvant options and its impact on the oncologic outcome is a matter of debate. With this background we carried out this study to analyze the rate of pathologic complete re-sponse (pCR) and its effect on recurrence in patients with carcinoma esophagus treated with various combinations of neoadjuvant chemotherapy/radiotherapy and surgery. Methods The records of all patients with carcinoma esophagus registered in our clinics between June 2012 and December 2014 were retrieved from a prospectively maintained database and were analyzed. of the 70 patients with histologically proven esophageal cancer who were treated with curative intent during this period, those with pCR (15) were followed up for a minimum of 5 years. These 15 patients are the subjects of this study. Results Forty eight (48) patients received neoadjuvant chemotherapy (NACT), 16 were treated with short course radiotherapy (SRT), and 3 patients received neoadjuvant chemoradiation (CRT). Four patients developed metastatic disease on neoadjuvant therapy. 66 patients (63 after neoadjuvant therapy and 3 upfront) underwent transthoracic esophagect-omy. Pathological CR was seen 12 patients (25%) in NACT-surgery arm, 2 (12%) in SRT-surgery and 1 (33%) in CRT-surgery groups. Three patients had postoperative mortality due to pulmo-nary complications. At 5 yrs, 14 out of 15 patients with pathological CR are alive and disease free. One patient developed brain metastases after 3 years and died. Conclusion Neoadjuvant therapy followed by radical surgery is a safe and effective treatment option for the management of carcinoma esophagus. Pathologic CR strongly correlates with recurrence-free survival. The relative significance of pCR after different types of neoadjuvant therapies need to be tested in future studies.

487 MINIMALLY INVASIVE ESOPHAGECTOMY AFTER A NEOADJUVANT PROTOCOL WITH INDUCTION CHEMOTHERAPY AND CHEMORADIATION

2021 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Flávio Sabino ◽  
Marco Guimarães-Filho ◽  
Luciana Ribeiro ◽  
Daniel Fernandes ◽  
Luis Felipe
Keyword(s):  
Esophageal Cancer ◽  
Minimally Invasive ◽  
Induction Chemotherapy ◽  
Squamous Cell ◽  
Minimally Invasive Esophagectomy ◽  
Type I ◽  
Gastrointestinal Malignancies ◽  
Surgical Specimen ◽  
Invasive Esophagectomy ◽  
Initial Results

Abstract   Neoadjuvant chemoradiation (CR) became the standard of care for the treatment of resectable esophageal cancer, but the survival rates are still worse than the observed in other gastrointestinal malignancies. The optimal neoadjuvant approach is still matter of debate. Based on these considerations, we started a phase II trial (QUIMERA) to investigate the safety and efficacy of preoperative induction chemotherapy followed by CR and minimally invasive surgery for esophageal cancer. We report the initial results. Methods Patients with confirmed squamous cell or adenocarcinoma of the thoracic esophagus or GEJ (Siewert type I or II), aged 18–75 years, with a PS 0–2, clinical stage cT1b-3 cN0–2 were eligible. After staging, patients received two cycles of IC with carboplatin (175 mg/m2) and paclitaxel (AUC = 5) on days 1 and 22, followed by radiotherapy (45 Gy (25 x 1.8 Gy)) and chemotherapy (carboplatin (AUC = 2) and paclitaxel (50 mg/m2) weekly for five weeks. After re-staging, patients with no stage M1 disease and/or inoperable T4 disease proceeded to surgery, minimally invasive esophagectomy in prone position, 8–12 weeks after the completion of chemoradiation. Results From March 2017 to December 2019, 86 were registered in the clinical trial. Forty-eight were excluded due to T4 or M1 disease, 26 patients finished the IC + chemoradiation protocol. Sixteen minimally invasive esophagectomy were performed. There were no conversions to open surgery. The surgical outcomes are presented in Table 1. The mean node count in the surgical specimen was 27 (13-49). A complete pathological response was observed in 6 (37,5%) cases (4 SCC; 2 Adenocarcinoma). Conclusion Our initial results are encouraging and suggests that IC followed by chemoradiation is a safe, feasible, active and well-tolerated regimen and that it may increase the PCR, especially for squamous cell carcinoma. The minimally invasive esophagectomy following the IC + CR was feasible, safe and had an adequate oncologic result. After the protocol completion there will be data available for a definitive evaluation of the procedure.

Utility of radiation after neoadjuvant chemotherapy for surgically resectable esophageal cancer.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 172-172
Author(s):  
Francis Igor Macedo ◽  
Kristin Kelly ◽  
Danny Yakoub ◽  
Dido Franceschi ◽  
Alan S Livingstone ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Neoadjuvant Therapy ◽  
Randomized Clinical Trials ◽  
Cox Regression ◽  
Independent Predictor ◽  
Locally Advanced ◽  
Pathological Response ◽  
Term Survival ◽  
Cancer Data

172 Background: Neoadjuvant chemotherapy (NAC) is the gold standard approach for locally advanced esophageal cancer (EC), however the addition of radiation remains largely controversial. We sought to investigate the role of neoadjuvant radiation in resectable EC by comparing outcomes of patients who underwent neoadjuvant chemotherapy with (NACR) or without radiation (NAC) using a large nationwide cohort. Methods: National Cancer Data Base (NCDB) was queried for patients with non-metastatic EC between 2010 and 2014. Kaplan-Meier, log-rank and Cox multivariable regression analysis were performed to calculate overall survival (OS). Logistic regression was used to identify factors associated with 90-day mortality and complete pathological response (pCR). Results: A total of 12,546 EC patients who underwent neoadjuvant therapy were included: the majority were males (84%), Caucasians (90.3%), and had adenocarcinoma (81.1%), cT3 (60.6%) and cN1 (49.1%). 11,269 (89.8%) patients had NACR, whereas 969 (7.7%), NAC alone. pCR rate was 14.1% (19.2%, NACR vs. 6.3%, NAC, p < 0.001). Neoadjuvant radiation was an independent predictor for improved pCR [HR 0.305, 95% CI 0.205-0.454, p < 0.001], however OS was similar in patients undergoing NAC with or without radiation (35.9 vs. 37.6 months, respectively, p = 0.393). This persisted regardless of tumor staging. There was a trend towards worse 90-day mortality after radiation (8.2%, NACR vs. 7.7%, NAC; HR 1.410, 95% CI 0.975-2.038, p = 0.068). In Cox regression, controlling for patient and disease-related factors, neoadjuvant radiation was an independent predictor of worse OS (HR 1.322, 965% CI 1.177-1.485, p < 0.001). Conclusions: This is the largest study comparing NACR versus NAC in resected EC. The addition of radiation to neoadjuvant chemotherapy is associated with improved pathological response rates, however it had deleterious effects in long-term and possibly, short-term survival. Our findings suggest that NAC without radiation may be the optimal neoadjuvant therapy in resectable EC, however further evidence with randomized clinical trials is warranted.

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