scholarly journals AGR2 – a Novel Predictor of Neoadjuvant Chemoradiotherapy Response in Esophageal Squamous Cell Carcinoma

2021 ◽  
Author(s):  
Chih-Hung Lin ◽  
Han-Ni Chuang ◽  
Tzu-Hung Hsiao ◽  
V. Bharath Kumar ◽  
Chiung-Hung Hsu ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Complete Response ◽  
Neoadjuvant Chemoradiation ◽  
Control Group ◽  
Gene Marker

Abstract BackgroundEsophageal squamous cell carcinoma (ESCC) still has a poor prognosis despite the use of multidisciplinary therapy. In the locally advanced stage, neoadjuvant chemoradiotherapy (nCRT) followed by surgery might provide survival benefits to some patients. MethodsIn this study, we aimed to identify biomarker to predict tumor response against neoadjuvant chemoradiotherapy (nCRT) by next-generation sequencing (NGS).ResultsOur data showed that 464 genes was differentially expressed ESCC specimens, in which AGR2 was 2.8 fold up-regulated in the patients with Non-complete response before nCRT than complete response group. In vitro study showed that, AGR2 was significantly reduced in AGR2 knockdown CE146T/VGH, TE2, and CE48T/VGH cells. MTT assay indicated that cell viability of AGR2-knockdown TE-2 cell line significantly decreased following 2.5µM cisplatin and 3µM 5-FU treatment. Furthermore, 6µM cisplatin and 20 µM 5-FU treatment greatly decreased AGR2-knockdown-CE48T/VGH, CE146T/VGH and TE-2 cells compared to control group. We also found in AGR2-knockdown cells, that protein level of p21 was increased in comparison with the control group. ConclusionsThis study suggest that AGR-2 as a promising and potential prediction gene marker dataset for response to neoadjuvant chemoradiation in ESCC.

scholarly journals Chemoradiation with Weekly Paclitaxel and Carboplatin in Esophageal Squamous Cell Carcinoma: A Prospective Study

2021 ◽  
Author(s):  
Deepa M. Joseph ◽  
Monica Irukulla Malik ◽  
Jyothi Jonnadula ◽  
Fayaz Ahmed ◽  
Deepthi Valiyaveettil
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Locally Advanced ◽  
Survival Rates ◽  
Complete Response ◽  
Median Number ◽  
Neoadjuvant Chemoradiation ◽  
Weekly Paclitaxel ◽  
Definitive Therapy

Abstract Objective Neoadjuvant chemoradiation (CRT) using paclitaxel and carboplatin has significantly improved the survival rates in carcinoma esophagus, especially in squamous cell carcinoma (SCC). This regimen has not been adequately explored prospectively as a definitive CRT strategy. Our aim was to evaluate the efficacy, toxicity, and compliance to this regimen in a prospective setting in locally advanced esophageal SCC. Materials and Methods Patients with locally advanced esophageal SCC were planned for definitive CRT by using weekly paclitaxel 50 mg/m2 and carboplatin area under curve 2 along with radical radiotherapy to a dose of 50.4 to 54 Gy. Treatment-related toxicity was assessed by using the common terminology criteria for Adverse Events Version 4.0, and the response was assessed by using endoscopy and computed tomography (CT) 4 to 6 weeks following CRT. The pathological response was documented for those who underwent surgery. Results Fifteen patients were included in the study, and all patients completed the planned course of radiation. The median number of chemotherapy cycles received was four. In total, 66% of the patients had delay or interruptions in chemotherapy, mostly due to neutropenia, and 66% of the patients had a clinical complete response (CR). Four patients underwent definitive esophagectomy, and the histopathology revealed pathologic CR. Overall CR rate was 80%. The median overall survival was 14 months, and 1-year survival was 57%. Conclusion Definitive CRT in esophageal SCC using weekly paclitaxel and carboplatin was relatively well tolerated with manageable toxicities and good clinical response rates. It may potentially represent a new standard of care as definitive therapy in the management of these tumors.

scholarly journals Antiemetic Prophylaxis for Chemoradiotherapy-induced Nausea and Vomiting (C-RINV) in Locally Advanced Head and Heck Squamous Cell Carcinoma: a Prospective Phase Ⅱ Trial

2021 ◽  
Author(s):  
Zekun Wang ◽  
Wenyang Liu ◽  
Jianghu Zhang ◽  
Xuesong Chen ◽  
Jingbo Wang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Locally Advanced ◽  
Intensity Modulated Radiotherapy ◽  
Complete Response ◽  
High Dose ◽  
Advanced Head ◽  
Free Response ◽  
Nausea And Emesis

Abstract Background There is sparse research reporting effective interventions for preventing nausea and emesis caused by concurrent chemoradiotherapy (CCRT) in locally advanced head and neck squamous cell carcinoma (LA-HNSCC). This phase Ⅱ trial was conducted to provide the direct evidence for the current practice of prescribing antiemetic in patients with LA-HNSCC receiving CCRT.Methods Treatment-naïve LA-HNSCC patients received intensity-modulated radiotherapy with concomitant cisplatin 100 mg/m² every 3 weeks for two cycles. All patients were given orally aprepitant 125 mg once on d1, then 80mg once on d2-5; ondansetron 8 mg once on d1; and dexamethasone 12 mg once on d1, then 8mg on d2-5. The primary endpoint was complete response (CR). Pursuant to δ=0.2 and α=0.05, the expected CR rate was 80%. Results A total of 43 patients with LA-HNSCC were enrolled. The median age was 53 years old, and 86.0% were male. All patients received radiotherapy and 86.0% of patients completed both cycles as planned. The overall CR rate was 86.0% (95% CI: 72.1-94.7). The CR rates for cycles 1 and 2 were 88.4% (95% CI: 74.9-96.1) and 89.2% (95% CI: 74.6-97.0). The complete protection rate in the overall phase was 72.1% (95% CI: 56.3-84.7). The emesis-free response and nausea-free response in overall phase were 88.4% (95% CI: 74.9-96.1) and 60.5% (95% CI: 44.4-75.0), respectively. The adverse events related to antiemetics were constipation (65.1%) and hiccups (16.3%), but both were grade 1-2. There was no grade 4 or 5 treatment-related adverse event with antiemetic usage. Conclusion The addition of aprepitant into ondansetron and dexamethasone provided effective protection from nausea and emesis in patients with LA-HNSCC receiving radiotherapy and concomitant high-dose cisplatin chemotherapy. Randomised phase 3 studies are required to further define the potential role of NK1RA in chemoradiotherapy setting.Trial registration: ClinicalTrials.gov, number NCT03572829. Registered 28 June 2018, https://clinicaltrials.gov/ct2/show/NCT03572829?term=NCT03572829&draw=2&rank=1.

scholarly journals Comparison of altered fractionation schedule with concurrent chemo-radiation for squamous cell carcinoma of head and neck

2020 ◽  
Vol 8 (8) ◽  
pp. 2834
Author(s):  
Mathew Varghese K. ◽  
Geeta S. Narayanan ◽  
Bhaskar Vishwanathan ◽  
Shashidhar V. Karpurmath ◽  
Soumya Narayanan
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Performance Status ◽  
Locally Advanced ◽  
Complete Response ◽  
Altered Fractionation ◽  
Fractionation Schedule ◽  
Nodal Burden

Background: Aim of the study was to compare the response of altered fractionation schedule with concurrent chemo-radiation in patients with primary and the nodal disease.Methods: Total of 40 patients (20 in each arm) with stage 1- 4 squamous cell carcinoma of the head and neck with a performance status of 0-2 (ECOG) were included in the study. Arm A was altered fractionation schedule where in patients received 6 fractions per week to a total dose of 6600 cGy in 33 fractions. In Arm B, patients received conventional radiotherapy with concurrent chemotherapy three weekly Inj. of cisplatin (100 mg/m2). Patients were evaluated for acute toxicity every week using the Acute Radiation Morbidity Scoring Criteria. The response was assessed after 6 weeks and 12 weeks post treatment using the RECIST criteria. Data was statistically analyzed.Results: Seventeen patients in Arm A and 18 patients in Arm B completed the treatment. At the end of three months, In Arm A, 7 patients had complete response and in Arm B, 9 patients had complete response of the primary (p>0.05).  When the complete nodal response was compared in both the arms, there was no difference (2 vs 4 in Arm A vs Arm B resp.). But there were more partial nodal responders in Arm B (p = 0.016). The acute toxicities were comparable in both the arms.Conclusions: Altered fraction radiotherapy can be used in early lesions with minimal nodal burden but with locally advanced disease or large nodal burden addition of chemotherapy should not be avoided.

scholarly journals Neoadjuvant Radiation with Concurrent 5-FU Resulting in Complete Pathologic Response in Stage IIIB Squamous Cell Carcinoma of the Urethra

2020 ◽  
Vol 2020 ◽  
pp. 1-3
Author(s):  
Krishna H. Suthar ◽  
Meghana Kesireddy ◽  
Mark Sides ◽  
Amit Correa ◽  
Aijan Ukudeyva ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cell Cancer ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiation ◽  
Pathologic Response ◽  
Stage Iiib ◽  
Rare Malignancy ◽  
Adjusted Incidence

Squamous cell carcinoma (SCC) of the urethra is a rare malignancy, comprising less than 1% of all malignancies. The annual age-adjusted incidence of urethral SCC is 4.3 per million in men and 1.5 per million in women. Due to the rarity of the disease, there are a limited number of prospective randomized controlled trials to evaluate the optimal management of locally advanced urethral SCC. Here, we present the case of a 47-year-old man with stage IIIB urethral squamous cell cancer that showed complete clinical and pathologic response to neoadjuvant chemoradiation with only 5-flurouracil after incomplete response to traditional chemotherapy with paclitaxel, ifosfamide, and cisplatin (TIP).

scholarly journals Pooled analysis of 115 patients from updated data of Epitopes-HPV01 and Epitopes-HPV02 studies in first-line advanced anal squamous cell carcinoma

2020 ◽  
Vol 12 ◽  
pp. 175883592097535 ◽  
Author(s):  
Stefano Kim ◽  
Aurélia Meurisse ◽  
Laurie Spehner ◽  
Morgane Stouvenot ◽  
Eric François ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Response Rate ◽  
Objective Response ◽  
Locally Advanced ◽  
Complete Response ◽  
Pooled Analysis ◽  
Term Survival ◽  
Anal Squamous Cell Carcinoma

Aims: The addition of docetaxel to cisplatin and 5-fluorouracil (DCF) has shown promising efficacy in advanced squamous cell carcinoma of the anus (SCCA). Preliminary results of Epitopes-HPV01 study showed a high rate of long-lasting complete response to DCF. The prospective, multicenter, Epitopes-HPV02 trial then confirmed the high efficacy of the modified DCF (mDCF) regimen in terms of complete response rate and long-term survival in metastatic or non-resectable locally advanced recurrent SCCA. Here, we present updated results of the Epitopes-HPV01 and Epitopes-HPV02 studies. Patients & methods: Epitopes-HPV01 is a prospective study performed by the regional cancer network of Franche-Comté, France. Epitopes-HPV02 is a phase II study supported by two French collaborative oncological groups, performed in 25 centers. Both studies included patients with metastatic, or with unresectable local recurrent SCCA, treated with DCF regimen. Results: In Epitopes-HPV01, 51 patients were enrolled between September 2012 and January 2019, and 49 patients were included for analysis; while 69 patients were included between September 2014 and December 2016 in Epitopes-HPV02, and 66 patients for analysis. Pooled analysis of 115 patients showed a median progression-free survival of 12.2 months [95% confidence interval (CI) 10.6–16.1] [11.0 months (9.3–16.0) in -HPV02, and 15.6 months (11.2–34.5) in -HPV01, ( p = 0.06)]. The median overall survival was 39.2 months (26.0–109.1) [36.3 in -HPV02 (25.2–NR), and 61.1 months (21.4–120.0) in -HPV01 ( p = 0.62)]. Objective response rate was 87.7% (90.9% in -HPV02 and 83.3% in -HPV01) with 40.3% of complete response (45.5% in -HPV02 and 33.3% in -HPV01). No differences were observed between standard DCF ( n = 54) and mDCF ( n = 58) in terms of OS ( p = 0.57) and PFS ( p = 0.99). 5-years PFS and OS rates were 24.5% and 44.4%, respectively, in the whole population. No treatment-related death was observed. Conclusion: Updated results of Epitopes-HPV01 and 02 studies, as well as the pooled analysis, confirm mDCF as a standard treatment in patients with advanced SCCA.

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