IMPORTANCE Multiple paclitaxel-based regimens are widely used in chemoradiation therapy against esophageal cancer, including regimens combining paclitaxel with fluorouracil, cisplatin, and carboplatin. However, which among these 3 regimens provides the best prognosis with minimum adverse events is still unknown. OBJECTIVE To compare the efficacy and adverse events of fluorouracil, cisplatin, and carboplatin in definitive chemoradiotherapy in patients with esophageal squamous cell carcinoma (ESCC). DESIGN, SETTING, AND PARTICIPANTSThis randomized clinical trial of patients with ESCC was conducted in 11 treatment centers in China. Eligible patients were aged 18 to 75 years and had histologically confirmed ESCC stages IIa to IVa with no prior treatment, Eastern Cooperative Oncology Group performance status of 2 or lower, and adequate organ functions. The study was conducted between July 2015 and February 2018, and the cutoff date for data analysis was August 31, 2020. INTERVENTIONS Patients with locally advanced ESCC were randomly assigned (1:1:1) to groups combining paclitaxel treatment with fluorouracil, cisplatin, or carboplatin. Patients in the cisplatin group were treated with 2 cycles of concurrent chemoradiotherapy followed by 2 cycles of consolidation chemotherapy with monthly paclitaxel plus cisplatin. For the fluorouracil group, patients were administered 6 cycles of weekly paclitaxel plus fluorouracil in concurrent chemoradiotherapy followed by 2 cycles of monthly paclitaxel plus fluorouracil in consolidation chemotherapy. Patients in the carboplatin group were treated with 6 cycles of weekly paclitaxel plus carboplatin in concurrent chemoradiotherapy followed by 2 cycles of monthly paclitaxel plus carboplatin in consolidation chemotherapy. All patients received radiotherapy of 61.2 Gy delivered in 34 fractions. MAIN OUTCOMES AND MEASURES The primary end point was overall survival (OS). The secondary end points were progression-free survival and adverse events. RESULTS Overall, 321 patients (median [IQR] age, 64 years [59-69 years]; 248 [77.3%] men) with ESCC from 11 centers were randomized into fluorouracil, cisplatin, or carboplatin groups between July 2015 and February 2018. Over a median (IQR) follow-up time of surviving patients of 46.0 months (36.6-53.0 months), the 3-year OS rates were 57.2% in the fluorouracil group, 60.1% in the cisplatin group, and 56.5% in the carboplatin group, respectively (fluorouracil vs cisplatin: HR, 1.06; 95% CI, 0.71-1.60; P = .77; fluorouracil vs carboplatin: HR, 0.94; 95% CI, 0.63-1.40; P = .77). The cisplatin group had significantly higher incidences of acute grade 3 or 4 neutropenia (69 events (continued) Key Points Question Which paclitaxel-based regimen, among fluorouracil, cisplatin, and carboplatin, provides the best prognosis with minimum adverse events for patients with locally advanced esophageal squamous cell carcinoma? Findings In this randomized clinical trial of 321 patients with esophageal squamous cell carcinoma treated in 11 cancer centers in China, th...
Radiation therapy is an important component of the comprehensive treatment of esophageal cancer. However, conventional radiation resistance is one of the main reasons for treatment failure. The superiority of heavy ion radiation in physics and biology has been increasingly highlighted in radiation therapy research. The Janus Kinase 2/Signal Transducer and Activator of Transcription 3 (JAK2/STAT3) pathway plays an important role in the occurrence, development and metastasis of esophageal squamous cell carcinoma (ESCC) and is related to the development of resistance to ionizing radiation in ESCC. Therefore, the aim of the present study was to investigate the relationship between carbon ion inhibition of the proliferation and metastasis of esophageal carcinoma cells and the JAK2/STAT3 signaling pathway. The results demonstrated that carbon ion beams significantly reduced cell viability and stimulated apoptosis in human ESCC cells in a dose-dependent manner. In addition, carbon ion beams induced G2/M phase cell cycle arrest in ESCC cells and inhibited tumor metastasis in a dose-dependent manner. Additionally, poorly differentiated KYSE150 cells were more sensitive to the same carbon ion beam dose than moderately differentiated ECA109 cells. Carbon ion beam exposure regulated the relative expression of metastasis-related molecules at the transcriptional and translational levels in ESCC cells. Carbon ion beams also regulated CDH1 and MMP2 downstream of the STAT3 pathway and inhibited ESCC cell metastasis, which activated the STAT3 signaling pathway. This study confirmed the inhibition of cell proliferation and the metastatic effect of carbon ion beam therapy in ESCC cells.
Objective: Postoperative radiotherapy for breast cancer is an effective way to control tumor recurrence; however, there are advantages and disadvantages to different radiotherapy techniques. This study compared dosimetry differences between intensity-modulated radiation therapy (IMRT) and three-dimensional conformal radiation therapy (3D-CRT) plans after radical surgery for left-sided breast cancer to provide guidance for clinicians to select a radiotherapy technique.Methods: A total of 50 women who received radiation therapy for left-sided breast cancer after radical surgery in Gansu Provincial Cancer Hospital between 9 January 2017 and 30 November 2017 were included. The prescription dose was 50 Gy/25f. IMRT and 3D-CRT treatment plans were designed for each patient on an Oncentra 4.1 planning system. Statistical analysis of the target dose distribution -conformal index, uniformity index, and irradiation doses to the ipsilateral lung, heart, left ventricle, humeral head, and thyroid -was carried out for the two groups and the differences were compared.Results: When comparing the two plans, the target V 95% (z = -5.739, P < 0.001), V 105% (t = -3.244, P = 0.002), V 110% (t = -9.420, P < 0.001), V 115% (z = −5.834, P < 0.001), conformal index (t = 27.711, P < 0.001), and uniformity index (t = -15.761, P < 0.001) for the IMRT plan were better than those for the 3D-CRT plan. Meanwhile, V 30 (t = -4.29, P < 0.001) and the maximum dose (z = -5.285, P < 0.001) of the ipsilateral lung, V 40 (z = -4.294, P < 0.001) and V 50 (z = -5.873, P < 0.001) of the heart, V 40 (z = -4.918, P < 0.001) and V 50 (z = -5.633, P < 0.001) of the left ventricle, and V 50 (z = -4.196, P < 0.001) of the humeral head in the IMRT plan were lower than those in the 3D-CRT plan. However, V 5 (t = 30.086, P < 0.001), V 10 (z = −6.154, P < 0.001), V 20 (t = 8.228, P < 0.001), and the mean dose (z = −4.156, P < 0.001) of the ipsilateral lung, V 30 (z = -4.407, P < 0.001) and the mean dose (t = 17.877, P < 0.001) of the heart, V 30 (z = −2.920, P = 0.003) and the mean dose (t = 15.324, P < 0.001) of left ventricle, the mean dose (z = −6.144, P < 0.001) of the humeral head, and V 40 (z = -6.154, P < 0.001) and the mean dose (z = -5.643, P < 0.001) of the thyroid in the IMRT plan were higher than those in the 3D-CRT plan. There was no statistically significant difference in the V 50 (t = 0.825, P = 0.413) of the thyroid between the IMRT and 3D-CRT plans.
Background: To evaluate locoregional failure and its impact on survival by comparing involved field irradiation (IFI) with elective lymph node irradiation (ENI) for patients with esophageal squamous cell cancer who underwent post-operative radiotherapy. Methods and Materials: The enrolled patients were randomized allocated to IFI or ENI group. CTV of IFI was generated according to pre-operative primary tumor location and post-operative pathological characters and positive LNs regions. CTV of ENI was generated according to pre-operative tumor position to administer selective lymph node irradiation. Radiotherapy planning was delivered using either 3D-CRT or IMRT. Results: A total of 57 patients were enrolled, 28 patients in ENI group and 29 patients in IFI group. There were not statistical differences between two groups in baseline (p>0.05). The initial locoregional failure rate was 17.9 % in ENI arm and 20.7% in IFI arm respectively (p=0.085). The 1-, 3-, and 5-year Progression-free Survival (PFS) were 63.2, 43.5, and 21.8 % in ENI arm versus 78.2, 60.1, and 55.1% in IFI arm (p =0.038). The 1-, 3-, and 5-year overall survival (OS) were 78.6, 46.9, and 23.5 % in ENI arm versus 72.9, 59.7, and 54.3 % in IFI arm (p=0.06). Acute radiation pneumonitis (p=0.005) and hematological toxicities (p =0.029) also showed statistical differences between groups, ENI arm was more than IFI arm. Conclusions: The results indicated that IFI tended to improve survival and reduce toxicities for patients with operative ESCC and did not increase locoregional failure compared to ENI. It is thus suggested that IFI for ESCC PORT is worthy of clinical recommendation and further study.
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