1432P Efficacy and safety of large-field postoperative radiotherapy using 3D radiation technique for locally advanced thoracic esophageal squamous cell carcinoma: A phase II clinical trial

BackgroundThis trial aims to explore the feasibility and safety of postoperative radiotherapy covering all regional lymph node areas for locally advanced thoracic esophageal squamous cell carcinoma patients treated with intensity-modulated radiation therapy (IMRT).MethodsThis was a single-center single-arm, phase II clinical trial initiated in 2014. Patients who were treated with radical transthoracic resection and had negative margins within 3 months and histologically confirmed esophageal squamous cell carcinoma (pT3-4 or N+, M0 determined by the 7th edition of the AJCC guidelines) were recruited in this trial. Postoperative radiotherapy was performed with a total dose of 40 Gy in 20 fractions using IMRT. Clinical target volumes (CTVs) included the tumor bed, anastomosis, bilateral supraclavicular region, mediastinal lymph nodes, left gastric lymph nodes and celiac trunk lymph nodes. The primary endpoint was the 2-year local control rate, and the secondary endpoints were overall survival (OS) and adverse events (AEs).ResultsA total of 70 eligible patients were recruited from 2014 to 2016. The 2-year local control rate, as the primary endpoint, was 67.3%. In addition, the median OS was 57.0 months, with 1-year and 3-year OS rates of 92.8% and 60.9%, respectively. Among the patients, 28/40 (40%) developed locoregional recurrence, with 25.7% involving hematogenous recurrences. All reported AEs occurred during the course of IMRT or within 6 months thereafter. None of them suffered grade 4 hematological or nonhematological AEs. Nearly all patients completed the entire course of postoperative radiotherapy, with a completion rate of 97.1%.ConclusionFor an extensive target volume, 40 Gy is feasible and shows acceptable toxicity in patients with locally advanced thoracic esophageal squamous cell carcinoma, although the local recurrence rate is relatively high. Our findings provide a basis for further exploration of high-dose radiation with extensive CTV combined with chemotherapy.Clinical Trial Registration[http://www.clinicaltrials.gov/ct2/results?cond=&term=NCT02384811&cntry=&state=&city=&dist=], identifier [NCT02384811].

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A phase II study of early FDG-PET evaluation after one-cycle chemotherapy in patients with locally advanced esophageal squamous cell carcinoma treated with neoadjuvant chemoradiotherapy: Final report.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.4042 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 4042-4042

Author(s):

Ta-Chen Huang ◽

Chia-Chi Lin ◽

Kai-Yuan Tzen ◽

Yun-Chun Wu ◽

Jason Chia-Hsien Cheng ◽

...

Keyword(s):

Clinical Trial ◽

Squamous Cell Carcinoma ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Phase Ii ◽

Squamous Cell ◽

Fdg Pet ◽

Locally Advanced ◽

Neoadjuvant Chemoradiotherapy ◽

Final Report

4042 Background: The optimal use of the metabolic tumor response measured by 18fluorodeoxyglucose positron emission tomography (FDG-PET) in the treatment of esophageal cancer is currently unknown. We launched a phase II clinical trial to evaluate the early metabolic response to one-cycle chemotherapy in locally advanced esophageal squamous cell carcinoma (ESCC) patients, who subsequently received neoadjuvant chemoradiation (neo-CRT) followed by surgery. Methods: ESCC patients with stage T3 or N1M0 or M1a (AJCC, 6th edition) were enrolled to receive one-cycle chemotherapy, day 1 and 8 doses of paclitaxel, cisplatin, and 24-hour infusional 5-fluorouracil and leucovorin, followed by paclitaxel/cisplatin- based 40Gy neo-CRT and surgery. FDG-PET was performed at baseline and day 14 of the one-cycle chemotherapy. The primary endpoint is pathological complete response (pCR) to neo-CRT. We hypothesized that early PET responders, defined as > 35% reduction of maximum standardized uptake value (SUVmax) from the baseline, would significantly improve pCR. Results: Between Feb 2008 and Mar 2012, 66 patients (M: F = 61: 5) were enrolled. Their clinical stages were: II or III, 56; IVA, 10. Forty seven received surgery. The pCR rate per surgical population was 34.0%. The median progression-free survival (PFS) and overall survival (OS) for the whole study group was 16 months (95% CI 9-27) and 22 months (95% CI 16-40), respectively. A total of53 patients were evaluable for PET response. The early PET response was not associated with high pCR rate or better survivals. However, in an exploratory analysis, the post-chemotherapy SUVmax was an independent prognostic factor for pCR, PFS and OS. A predictive model for pCR composed of weight loss and the post-chemotherapy SUVmaxwas established with an AUC of 0.84. Conclusions: Our study failed to validate the predictive value of predefined early PET response to one-cycle chemotherapy for pCR to neo-CRT in locally advanced ESCC patients. However, the FDG-PET SUVmax after one-cycle chemotherapy may have prognostic and predictive significance, and may be explored in further studies. Clinical trial information: NCT01034332.

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Paclitaxel in combination with cisplatin and 5-fluorouracil (TPF) induction chemotherapy for locally advanced borderline-resectable esophageal squamous cell carcinoma: A phase II clinical trial

Annals of Oncology ◽

10.1093/annonc/mdz247.094 ◽

2019 ◽

Vol 30 ◽

pp. v297

Author(s):

Y. Li ◽

Z. Wang ◽

H. Yang ◽

Q. Li ◽

H. Liu ◽

...

Keyword(s):

Clinical Trial ◽

Squamous Cell Carcinoma ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Induction Chemotherapy ◽

Phase Ii ◽

Squamous Cell ◽

Locally Advanced ◽

Borderline Resectable ◽

Resectable Esophageal

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TENERGY: Multicenter phase II study of atezolizumab monotherapy following definitive chemoradiotherapy with 5-FU plus cisplatin in patients with locally advanced esophageal squamous cell carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.tps4141 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. TPS4141-TPS4141 ◽

Cited By ~ 1

Author(s):

Hideaki Bando ◽

Daisuke Kotani ◽

Takahiro Tsushima ◽

Hiroki Hara ◽

Shigenori Kadowaki ◽

...

Keyword(s):

Clinical Trial ◽

Squamous Cell Carcinoma ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Phase Ii ◽

Squamous Cell ◽

Locally Advanced ◽

Human Leukocyte ◽

Background Information ◽

Definitive Chemoradiotherapy

TPS4141 Background: The standard treatment for patients with unresectable locally advanced esophageal squamous cell carcinoma (ESCC) is definitive chemoradiotherapy (CRT) using 5-FU plus cisplatin. However, complete response (CR) rates are only 11% to 25%, and median overall survival (OS) is 9 to 10 months. The improved therapeutic efficacy of combining immunotherapy with radiation has been gaining interest. Our basic research suggested that sequential treatment with anti-PD-L1 agents soon after completion of CRT is the best combination. Twelve months of anti-PD-L1 antibody following platinum-based CRT significantly improved progression-free survival (PFS) and OS in patients with locally advanced non-small cell lung cancer (Antonia SJ, et al. N Engl J Med. 2018). Based on this background information, we have planned a phase II clinical trial to evaluate the safety and efficacy of atezolizumab monotherapy following definitive CRT in patients with locally advanced ESCC. Methods: The main inclusion criteria are unresectable locally advanced ESCC without distant metastasis, completion of treatment with 60 Gy of radiation plus two concomitant cycles of chemotherapy (cisplatin 70 mg/m2 on day 1 and 5-FU 700 mg/m2 on days 1–4, every 28 days), and adequate organ function. Within 4 weeks after CRT, patients will be registered in the study and started on 1200 mg of atezolizumab every three weeks until 12 months or disease progression. The primary endpoint is the CR rate by the investigator’s assessment. Overall response rate, PFS, OS, treatment-related adverse events, and CR rate by central assessment are secondary endpoints. A total of 50 patients will be enrolled, including 40 with primary locally advanced ESCC and 10 with postoperative loco regionally recurrent ESCC. As an exploratory biomarker study, biopsies from the primary site and blood collections will be performed at 3 time points (before CRT, after CRT, and four weeks after the start of atezolizumab). We will analyze the phenotype of immune-competent cells, neoantigens, tumor mutation burden, PD-L1 status, and Human Leukocyte Antigen haplotyping. Clinical trial information: UMIN000034373.

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