Yonghong Hu

We conducted a Phase II study to assess the efficacy and toxicity of nab-paclitaxel (nab-PTX) and cisplatin in combination with concurrent radiotherapy in

Background: This phase I study aimed to assess the safety, dose‐limiting toxicity (DLT), maximum tolerated dose (MTD) and preliminary effect of nanoparticle albumin‐bound (nab)‐paclitaxel in combination with concurrent chemoradiotherapy in patients with locally advanced esophageal squamous cell carcinoma (ESCC).Methods: Patients with locally advanced ESCC who were ineligible or refused surgery were enrolled. Nab‐paclitaxel (60 mg/m², 75 mg/m², and 90 mg/m²) and cisplatin (25 mg/m²) were administered intravenously weekly on days 1, 8, 15, 22, and 29 on the basis of the 3 + 3 dose escalation method. The total dose of radiation was 50–64 Gy. The primary endpoint was the safety of chemotherapy.Results: The study enrolled 12 patients across three dose levels. No treatment‐related deaths occurred. One patient in the 60 mg/m² dose level occurred dose‐limiting Grade 3 febrile neutropenia. No DLT was found in the 90 mg/m² dose level thus the MTD was not reached. The phase II study's recommended dose was 75 mg/m² based on the available preclinical and clinical data including pharmacokinetics, pharmacodynamics, efficacy, and toxicity. The frequent hematologic toxicities were leukocytopenia (Grade 1–2 of 66.7% and Grade 3–4 of 33.3%), neutropenia (Grade 1–2 of 91.7% and Grade 3–4 of 8.3%). Nonhematologic toxicities were mild and manageable. Overall response rate (ORR) of all patients achieved 100%.Conclusions: Weekly schedule of cisplatin and nab‐paclitaxel in combination with concurrent radiotherapy showed manageable toxicities and promising antitumor activity in patients with locally advanced ESCC. The recommended dose of nab‐paclitaxel for further studies is 75 mg/m².

The purpose of this study was to compare the survival and toxicities in cervical esophageal squamous cell carcinoma (CESCC) treated by concurrent chemoradiothrapy with either three-dimensional conformal radiotherapy (3D-CRT) or intensity-modulated radiotherapy (IMRT) techniques. A total of 112 consecutive CESCC patients were retrospectively reviewed. 3D-CRT and IMRT groups had been analyzed by propensity score matching method, with sex, age, Karnofsky performance status, induction chemotherapy, and tumor stage well matched. The Kaplan-Meier method and Cox proportional hazards model were used for overall survival (OS) and progression-free survival (PFS). Toxicities were compared between two groups by Fisher exact test. With a median follow-up time of 34.9 months, the 3-year OS (p=0.927) and PFS (p=0.859) rate was 49.6% and 45.8% in 3D-CRT group, compared with 54.4% and 42.8% in IMRT group. The rates of grade ≥ 3 esophagitis, grade ≥ 2 pneumonitis, esophageal stricture, and hemorrhage were comparable between two groups, while the rate of tracheostomy dependence was much higher in IMRT group than 3D-CRT group (14.3% vs.1.8%, p=0.032). Radiotherapy technique (hazard ratio [HR], 0.09; 95% confidence interval [CI], 0.01 to 0.79) and pretreatment hoarseness (HR, 0.12; 95% CI 0.02 to 0.70) were independently prognostic of tracheostomy dependence. No survival benefits had been observed while comparing IMRT versus 3D-CRT in CESCC patients. IMRT with fraction dose escalation and pretreatment hoarseness were considered to be associated with a higher risk for tracheostomy dependence. Radiation dose escalation beyond 60 Gy should be taken into account carefully when using IMRT with hypofractionated regimen.

Lessons Learned Weekly treatment with 5‐fluorouracil and cisplatin, concurrent with radiotherapy, achieved promising response rates in patients with postoperative recurrent esophageal squamous cell carcinoma. Superior toxicity results were also found. Background Concurrent chemoradiotherapy (CCRT) is one of the treatment strategies for patients with esophageal squamous cell carcinoma (ESCC) with postoperative locoregional recurrence. However, the once every 3 weeks chemotherapy regimen causes a high incidence of toxicity. The aim of this study was to evaluate the efficacy and toxicity of weekly 5‐fluorouracil (5‐FU) and cisplatin concurrent with radiotherapy in postoperative locoregional recurrent ESCC. Materials and Methods Patients received four weekly chemotherapy cycles of cisplatin (25 mg/m², day 1) plus 5‐FU (1,176 mg/m², day 1–3), and concurrent with radiotherapy (50.4–60 Gy). The primary endpoint was objective response rate (ORR). Secondary objectives were toxicity, disease control rate (DCR), progression‐free survival (PFS), and overall survival (OS). Results Between January 2013 and December 2015, 48 patients were enrolled. The ORR was 68.8% (12 patients with complete response, 21 patients with partial response), with DCR 68.8%. No treatment‐related grade 4 adverse events occurred. Grade 3 hematologic toxicities were observed in eight (17%) patients. Grade 3 vomiting or esophagitis occurred in four (8%) patients each. The median PFS and OS were 13.94 months (95% confidence interval [CI], 0.75–51.05) and 27.43 months (95% CI, 5.278–49.58; Fig. 1). Conclusion Weekly 5‐FU and cisplatin concurrent with radiotherapy achieved a promising response rate and improved toxicity in patients with postoperative locoregional recurrent ESCC.

Background: Small cell carcinoma of the esophagus (SCCE) is characterized by its progressive feature and poor prognosis. There is no consensus on a standard therapeutic modality for SCCE. In this study, we aimed to characterize the outcomes of primary SCCE patients treated by radiation therapy as part of treatment and investigate prognostic factors.Methods: We retrospectively analyzed the data of 42 SCCE patients who were treated by RT as part of treatment at the Sun Yat-sen University Cancer Center from 2001 to 2014. The Kaplan-Meier and log-rank method were used to analyze survival. Cox’s hazard regression model was applied to determine prognostic factors.Results: Of the 42 enrolled patients, 25 had limited disease (LD) and 17 with extensive disease (ED). The overall response rate (CR + PR) was 60.0% (21/35). The median overall survival time (OS) for whole and LD group were 12.9 and 36.8 months. The 1-, 3- and 5-year OS rates of the whole cohort were 64.9, 31.3, and 13.9%, respectively. OS was significantly longer in patients with ECOG performance score (ECOG PS) < 2 (p = 0.001), lesion length ≤ 5 cm (p = 0.001), and LD (p = 0.049). In the patients with LD, multivariate analysis indicated that combined with chemotherapy (P = 0.046) and higher radiation dose (P = 0.027) predicted better prognosis in OS. The overall rate of grade 3–4 toxicities in the whole cohort was 37.5%. In total, 65% (17/26) patients with recurrent disease died with the metastasis with or without the primary recurrence.Conclusion: RT was one of the effective and safe treatments for locoregional control of SCCE. Lower ECOG PS score, shorter lesion length, treated with chemotherapy, and a higher dose of RT were identified as favorable independent prognostic factors.

Purpose To investigate the relationship between treatment-related lymphopenia and pathologic response to neoadjuvant chemoradiotherapy (CRT) in patients with esophageal squamous cell carcinoma (ESCC).

Concurrent chemotherapy (CCT) is used in locally advanced nasopharyngeal carcinoma (NPC) for improved local control, which could also be achieved by intensity‐modulated radiotherapy (IMRT). And for N2‐3 NPC, distant metastasis is the more important cause of death. This study aims to evaluate the value of CCT in N2‐3 NPC when neoadjuvant chemotherapy (NACT) of sufficient cycles is performed to eradicate distant metastasis. It enrolled 959 patients diagnosed with TxN2‐3M0 NPC from July 2011 to December 2015 and treated with NACT of 3‐4 cycles and IMRT. A propensity score matching (PSM) was made between patients treated with and without CCT (called the CCT and non‐CCT groups, respectively), using a series of clinical characteristics (age, gender, T stage, N stage, NACT regimen, and EBV DNA) as covariates. After PSM, the two groups of patients were compared on survivals and acute toxicities. The results indicated that no difference was seen in the overall, disease‐free, recurrence‐free or metastasis‐free survivals between the two groups. But compared with the CCT group, the non‐CCT group had a lower patient proportion of myelosuppression, nausea/vomiting, oral mucositis, cervical dermatitis, xerostomia, and grade 3/4 myelosuppression and oral mucositis (all P values were <0.001). Hence, CCT appeared to bring more acute toxicities, instead of survival benefit, to N2‐3 NPC patients treated with NACT of ≥3 cycles and IMRT. It should be used with cautions in these patients.

The incidence of elderly patients with esophageal cancer (OC) is increasing as the population ages. Until now, the treatment strategy in these patients has been unclear. The aim of our study was to assess the efficiency and tolerance of treatment with radiotherapy alone (RT alone), single‐agent‐based concurrent chemoradiotherapy (CCRT‐1), or double‐agent‐based concurrent chemoradiotherapy (CCRT‐2) in elderly patients (≥65 years) with OC. A total of 271 patients with OC aged 65 years or older were included in this study. The median overall survival (OS), median progression‐free survival (PFS), overall response rate (ORR), disease control rate (DCR), and treatment‐related toxicities were assessed. The median OS time for all patients was 23.6 ± 2.3 months, with 2‐year survival rates of 48.0 ± 3.0%. The median PFS time was 13.6 ± 1.3 months with the 2‐year PFS rate was 33.0 ± 4.0%. Among patients who received CCRT‐1, better OS, and PFS were found in patients who received docetaxel than in patients received fluorouracil and platinum. In a subgroup analysis, 118 patients who underwent RT alone had a median OS time of 15.6 ± 1.9 months and median PFS time of 10.4 ± 0.9 months. The median OS time of patients who received CCRT‐1 was 28.8 ± 10.1 months compared with 27.8 ± 2.5 months for the patients treated with CCRT‐2 (P = 0.537). The similar results were observed for median PFS, with 16.5 ± 3.2 months in the CCRT‐1 group and 17.0 ± 2.0 months in the CCRT‐2 group (P = 0.321). Grade ≥3 leukocytopenia and grade ≥2 weight loss during treatment occurred in 40.6% and 17.9% of patients, respectively, in the CCRT‐2 group, which was higher than that observed in the CCRT‐1 group. Our results suggested that CCRT could be considered as an acceptable treatment for elderly patients with OC. The CCRT‐1 group presented with a lower incidence of treatment toxicities but comparable survival outcomes, compared to the CCRT‐2 group. Docetaxel was superior to fluorouracil and platinum in terms of OS.

To investigate the incidence of radiation esophagitis (RE) and tumor local control using esophagus sparing technique in locally advanced non-small cell lung cancer (LANSCLC) treated by simultaneous integrated boost intensity-modulated radiation therapy (SIB-IMRT) and concurrent chemotherapy. Eighty-seven patients with stage IIIA/B NSCLC who received definitive SIB-IMRT and concurrent chemotherapy had been divided into two groups: 1.with esophagus sparing technique; 2.without esophagus sparing technique. Chi-square test was performed to compare sex, clinical stage, histology, concurrent chemotherapy, RE and nutrition status between two groups. T-test was used to compare the dosimetric parameters. Overall survival (OS) and loco-regional failure free survival (LRFS) were calculated by the Kaplan–Meier method and compared by a log-rank test. There were 44 patients in the esophagus sparing group and 43 in the non-sparing group. The incidence of severe RE (Grade 3) was significantly lower in patients with esophagus sparing technique (p = 0.002). Patients in esophagus sparing group had better nutrition status (p = 0.045). With a median follow-up of 18 months (range 1–51 months), the 1-year, 2-year and 3-year OS of all the patients was 86.6, 65.4 and 43.7%. The 1-year, 2-year LRFS was 78.4, 65.9%. OS time (p = 0.301) and LRFS (p = 0.871) was comparable between two groups. Esophagus-sparing technique is an effective and essential method to limit RE in LANSCLC treated by SIB-IMRT and concurrent chemotherapy without compromising local control.

Brain metastasis is very rare in esophageal squamous cell carcinoma (ESCC). We retrospectively analyzed 4494 patients diagnosed with ESCC between 2010 and 2015 at a single institute; 15 of these patients developed brain metastases. All 15 patients had neurologic symptoms and were diagnosed by imaging or biology. Of the 15 patients, 67% had a solitary brain lesion and 73% had lesions larger than 3 cm. After treatment of the brain lesions, including surgery (53%) or stereotactic radiotherapy with or without whole brain radiation (20%), the median progression free survival time and the 2-year overall survival rate calculated from diagnosis of brain metastasis were 14.4 months and 36%, respectively. A graded prognostic assessment (GPA) score > 2.0 was associated with significantly better overall survival. Patients with brain metastases from ESCC achieve good overall survival after appropriate treatment of the brain lesion(s); GPA score may represent a prognostic factor for treatment decision-making.