scholarly journals GASC1-Adapted Neoadjuvant Chemotherapy for Resectable Esophageal Squamous Cell Carcinoma: A Prospective Clinical Biomarker Trial

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Ruinuo Jia ◽  
Youjia Mi ◽  
Xiang Yuan ◽  
Dejiu Kong ◽  
Wanying Li ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Neoadjuvant Chemotherapy ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Tumor Regression ◽  
Objective Response ◽  
Tumor Regression Grade ◽  
Potential Biomarker ◽  
Significant Difference

Neoadjuvant chemotherapy (NCT) is a standard care for esophageal squamous cell carcinoma (ESCC), but the efficacy is unsatisfactory. Cancer stem cells (CSCs) play key roles in chemotherapy resistance. Gene amplified in squamous cell carcinoma 1 (GASC1) is a neoteric gene in stemness maintaining of ESCC. We aimed to reveal whether GASC1 could be a predictive biomarker for NCT in ESCC. ESCC patients (T2-4N0-2M0) were evaluated for GASC1 expression using immunohistochemical staining and classified as GASC1-low group (GLG) and GASC1-high group (GHG). NCT was delivered in two cycles and then the surgery was completed. Primary endpoints were tumor regression grade (TRG) and objective response rate (ORR); secondary endpoints were radical surgical resection (R0) rate and three-year overall survival (OS). 60 patients were eligible with evaluable outcomes: 24 in GHG and 36 in GLG. Between GHG and GLG, TRG1, TRG2, TRG3, and TRG4 were 0 : 16.7%, 20.8% : 41.7%, 58.3% : 36.1%, and 20.8% : 5.6%, respectively (P=0.006); ORR and R0 rate were 33.3% : 69.4% (P=0.006) and 75% : 94.4% (P=0.046), respectively; the median OS was 20 : 32 (months) (P=0.0356). No significant difference in the three-year OS was observed between GHG and GLG: 29.2% : 41.7% (P=0.24). Furthermore, the GASC1 expression level was associated with poor OS independent of other factors by univariate and multivariate analyses. Therefore, GASC1 might be a potential biomarker to predict NCT efficacy for ESCC.

FA06.01: CLINICAL EFFECT OF NEOADJUVANT CHEMOTHERAPY OF ESOPHAGEAL SQUAMOUS CELL CARCINOMA FOR SUPERFICIAL PHARYNGEAL SQUAMOUS CELL CARCINOMA

2018 ◽  
Vol 31 (Supplement_1) ◽  
pp. 11-11
Author(s):  
Hiroki Ishida ◽  
Hirofumi Kawakubo ◽  
Shuhei Mayanagi ◽  
Kazumasa Fukuda ◽  
Rieko Nakamura ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Neoadjuvant Chemotherapy ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Median Duration ◽  
Systemic Chemotherapy ◽  
Tumor Regression ◽  
Flat Type ◽  
Pharyngeal Squamous Cell Carcinoma

Abstract Background Esophageal squamous cell carcinoma (ESCC) is often synchronously accompanied by pharyngeal squamous cell carcinoma (PSCC). However, the treatment strategies for these cancers have not been established. Neoadjuvant chemotherapy is the standard treatment for advanced ESCC and is also effective for PSCC patients. However, few studies have focused on the efficacy of systemic chemotherapy for patients with superficial PSCC. Methods We retrospectively examined 22 cases of superficial PSCC that occurred in 14 patients with ESCC who received neoadjuvant therapy between January 2011 and June 2017. Results Of the 14 patients, 13 (93%) were male, and the median age was 63.5 years (range: 35–74 years). The clinical stage of ESCC was II for 7, III for 5, and IVB for 2 (AJCC 8th staging system). The PSCC origin included the oropharynx in 9 lesions (40.9%) and the hypopharynx in 13 lesions (59.1%). Macroscopic type was classified as protruding (type1 or 0-I) for 2, superficial elevated (0-IIa) for 5, superficial flat (0-IIb) for 13, and superficial depressed (0-IIc) for 2. The estimated depth of invasion was EP in 12 lesions, SEP in 8 lesions, and MP in 2 lesions. FP regimen was administered to 11 patients in 15 lesions and DCF to 3 patients in 7 lesions. One patient had concurrent chemoradiotherapy. Chemotherapy for PSCC resulted in CR in 10 lesions (45.4%). In CR, 9 of 10 lesions were of superficial flat type. All non-CR lesions also had tumor regression. In the CR patients, 5 lesions(50%) had local recurrence, and the median duration until recurrence was 4 months (range: 4 to 17 months). Endoscopic resection(ER) for PSCC was performed in the 13 lesions after esophagectomy. The median duration after diagnosis was 7 months (range: 3 to 20 months). Conclusion Systemic chemotherapy of ESCC has tumor regression potential for superficial flat-type PSCC with clinical tumor invasion in EP or SEP. Although chemotherapy for PSCC results in non-CR, additional ER is quite effective. Because half of the CR lesions had recurrence, strict follow-up and observation of the pharynx are reasonable options for patients with ESCC. Disclosure All authors have declared no conflicts of interest.

A preoperative nomogram for tumor regression grade following induction chemotherapy for esophageal squamous cell carcinoma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15525-e15525
Author(s):  
Xiaozheng Kang ◽  
Liang Dai ◽  
Wanpu Yan ◽  
Yongbo Yang ◽  
Haitao Zhou ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Induction Chemotherapy ◽  
Squamous Cell ◽  
Tumor Regression ◽  
Locally Advanced ◽  
Continuous Distribution ◽  
Tumor Regression Grade ◽  
Regression Grade

e15525 Background: To (1) evaluate the continuous distribution of tumor regression grade (TRG) in resection specimens after induction chemotherapy for locally advanced esophageal squamous cell carcinoma (ESCC), (2) determine the effects of TRG on survival after esophagectomy, and (3) identify preoperative predictors of TRG. Methods: From June 2001 to October 2012, 212 patients underwent induction chemotherapy followed by esophagectomy for locally advanced ESCC. TRG, assessed as the percentage of residual primary ESCC cells in resection specimens, was classified histologically by pathologists. Random Forest technology was used for data analysis. A nomogram was developed allowing prediction of TRG through use of preoperative clinical factors for patients with clinically locally advanced ESCC who are candidates for treatment with a radical esophagectomy. Results: Twenty-four specimens (11%) had no residual primary cancer (ypT0), 39 (18%) had 1% to 10% residual cancer, 48 (23%) had 11% to 50%, 101 (48%) had more than 50%. Survival was worse with increasing residual primary ESCC, plateauing at 50%. Poorer TRG was associated with worse 3-year overall survival. Better pathologic grade (G), larger number of pack year smoking, fewer cycles of induction chemotherapy, lower level of creatinine, younger age, greater tumor length and clinical T stage were associated with poorer TRG. Conclusions: Better TRG in response to preoperative chemotherapy is associated with a linear increase in survival after esophagectomy for locally advanced ESCC. A nomogram has been developed that can be used to predict TRG. Therefore, for patients with poorer TRG, the role of adjuvant therapy needs to be further assessed in an attempt to improve survival.

Neoadjuvant PD-1 blockade in combination with chemotherapy for patients with resectable esophageal squamous cell carcinoma.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 220-220
Author(s):  
Chao Cheng ◽  
Weixiong Yang ◽  
Wenfang Chen ◽  
Sai-Ching Jim Yeung ◽  
Xiangbin Xing ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Squamous Cell Carcinoma ◽  
Adverse Events ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Tumor Regression ◽  
Objective Response ◽  
Neoadjuvant Treatment ◽  
R0 Resection

220 Background: Programmed death-1 (PD-1) blockade may induce tumor regression in patients with advanced esophageal squamous cell carcinoma (ESCC), but little is known about the efficacy of PD-1 blockade in neoadjuvant therapy of resectable ESCC. Methods: Under an approved clinical trial protocol, a pilot study was conducted by enrolling patients with untreated, resectable (stage II or IIIA) ESCC. After written informed consent, each patient received two 21-day cycles of neoadjuvant treatment with camrelizumab (200mg), albumin-paclitaxel (260mg/m2) and carboplatin (area under the curve = 5) followed by surgical resection about 6 weeks after the first dose. The primary end points were safety and feasibility. We also reported the objective response rate (ORR), disease control rate (DCR) and tumor pathological response. Results: Between January 19, 2020, and July 21, 2020, we assessed 35 patients for screening, of whom 20 patients were enrolled. Neoadjuvant combination of camrelizumab, carboplatin and albumin-paclitaxel had an acceptable side-effect profile, and was not associated with delays in surgery. The ORR was 85%, and the DCR was 100%. Eighteen (90%) patients were taken into the surgery, and all of them successfully underwent R0 resection. Five (5/18 = 27.8%) patients had a pathological complete response (pCR), and eight (44.4%) patients had major pathological responses (MPR).The most common treatment-related grade 1–2 adverse events were leukopenia (12, 60%), neutropenia (11, 55%) and nausea (8, 40%). Two (10%) patients suffered grade 3 neutropenia. There was no grade 4 adverse events and treatment-related deaths. Conclusions: Neoadjuvant camrelizumab plus carboplatin and albumin-paclitaxel had manageable treatment-related toxic effects, did not delay surgery. This regimen induced pCR or MPR in 72.2% of resected tumor, demonstrating its antitumor efficacy in resectable ESCC. Clinical trial information: ChiCTR2000028900.

scholarly journals Significance of chemotherapy-free interval and tumor regression grade in patients with recurrent esophageal squamous cell carcinoma receiving chemotherapy with fluorouracil and platinum after esophagectomy following preoperative chemotherapy

Esophagus ◽  
2021 ◽  
Author(s):  
Mashiro Okunaka ◽  
Daisuke Kotani ◽  
Ken Demachi ◽  
Hisashi Fujiwara ◽  
Shingo Sakashita ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Preoperative Chemotherapy ◽  
Squamous Cell ◽  
Recurrent Disease ◽  
Tumor Regression ◽  
Tumor Regression Grade ◽  
Free Interval ◽  
Regression Grade

Abstract Background In Japan, standard treatment for locally advanced esophageal squamous cell carcinoma (ESCC) includes preoperative chemotherapy with fluorouracil plus cisplatin followed by esophagectomy. However, its efficacy is unclear in patients with recurrent disease with < 6 months of chemotherapy-free interval (CFI) after preoperative chemotherapy followed by esophagectomy and in those with ≥ 6 months of CFI and poor pathological response to prior preoperative chemotherapy. Method We retrospectively evaluated the efficacy of fluorouracil plus platinum in patients with recurrent ESCC who received preoperative chemotherapy followed by curative esophagectomy. Results Among 105 patients with recurrent ESCC after preoperative chemotherapy followed by esophagectomy, a total of 55 patients received fluorouracil plus platinum for recurrent disease. Patients with a CFI < 6 months (n = 20) had significantly shorter overall survival (OS) (median, 7.1 vs 14.5 months, P = 0.008) compared with those with a CFI ≥ 6 months (n = 35). Multivariate analysis showed that OS was worse in patients with a CFI < 6 months or a tumor regression grade (TRG) ≤ 1a. Furthermore, in patients with a CFI ≥ 6 months, TRG ≤ 1a was associated with significantly shorter OS (11.1 months vs. not reached, P = 0.001). Conclusion Fluorouracil plus platinum was ineffective for recurrent ESCC in patients with a CFI < 6 months and in those with a CFI ≥ 6 months and a TRG ≤ 1a. Alternate regimens including nivolumab or pembrolizumab might be considered for the treatment for recurrence in these patients.

Nivolumab in advanced esophageal squamous cell carcinoma (ATTRACTION-1/ONO-4538-07): Minimum of five-year follow-up.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 207-207
Author(s):  
Ken Kato ◽  
Yuichiro Doki ◽  
Takashi Ura ◽  
Yasuo Hamamoto ◽  
Takashi Kojima ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Disease Progression ◽  
Squamous Cell ◽  
Group Performance ◽  
Objective Response

207 Background:ATTRACTION-1/ONO-4538-07 (AT-1), an open-label, single-arm, multicenter phase 2 clinical trial conducted in Japan, evaluated the clinical activity and safety of nivolumab in patients with advanced esophageal squamous cell carcinoma (ESCC) refractory/intolerant to fluoropyrimidine-, platinum-, and taxane-based chemotherapy. We previously reported the 2-year follow-up findings of AT-1, in which nivolumab demonstrated antitumor activity with a manageable safety profile for these patients. Here we report the final findings from AT-1 at a minimum follow-up of 5 years. Methods:Patients aged ≥20 years with an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-1 received 3 mg/kg nivolumab intravenously every 2 weeks in 6-week cycles until disease progression or unacceptable toxicity. The primary endpoint was centrally-assessed objective response rate (ORR), defined as the proportion of patients whose best overall response was either a complete or partial response. Secondary endpoints included overall survival (OS), investigator-assessed ORR, progression-free survival (PFS), change in tumor burden, time to response, time to disease progression, and duration of response. Results:Between February 25 and November 14, 2014, a total of 65 patients were enrolled. Sixty-four patients were evaluated for the efficacy, and all patients were evaluated for the safety. At the final database lock on August 6, 2020, 11 (17.2%, 95% confidence interval [CI] 9.9-28.2) of 64 patients had an objective response by central assessment. The median OS was 10.8 months (95% CI, 7.4-13.9), and the estimated 5-year OS rate was 6.3% (95% CI, 2.0-14.0). The median PFS was 1.5 months (95% CI, 1.4-2.8), and the estimated 5-year PFS rate was 6.8% (95% CI, 2.2-15.1). Treatment-related adverse events that occurred with a frequency of > 10% were diarrhea and rash. The presentation will include characteristics of long-term survivors as well as detailed efficacy and safety data of nivolumab. Conclusions:This final assessment represents the longest follow-up of patients with advanced ESCC treated with nivolumab. Nivolumab demonstrated continued long-term efficacy in these patients based on a minimum of 5-year long-term survival update of AT-1. Furthermore, no new safety signals with nivolumab were identified during long-term follow-up. These findings are consistent with those of nivolumab monotherapy for various types of cancer. Clinical trial information: No.142422.

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