Long-term clinical outcomes and prognosis after definitive radiotherapy for patients with cervical esophageal squamous cell carcinoma: a single-institution retrospective study.

Background: Definitive radiotherapy has become a more common treatment for cervical esophageal squamous cell carcinoma (CESCC), but data about long-term clinical outcomes is still relatively sparse. The purpose of this study was to describe long-term clinical outcomes after definitive radiotherapy for CESCC, and identify the prognostic factors influencing these outcomes. Methods: We retrospectively analyzed all patients who received definitive radiotherapy for CESCC at our institution between 2006 and 2014. The overall survival (OS) rate, locoregional failure-free survival (LRFFS) rate, and toxicities were retrospectively evaluated during long-term follow-up. Univariate and multivariate analyses were performed to identify prognostic factors. Results: A total of 120 patients were included for analysis. The median prescribed radiation dose for the gross tumor and metastatic lymph nodes was 60 Gy. Elective nodal irradiation (ENI) was performed on 99 patients (83%); 90 patients (75%) received concurrent chemotherapy. The OS rates were 22.7% at 5 years and 14.9% at 8 years. The LRFFS rates at 3, 5, and 8 years were 27.5%, 21.7%, and 15.0%, respectively. The univariate analysis suggested that N classification and non-regional lymph node metastasis (M1Lym) status were independent risk factors for overall survival (P<0.01). A dose of more than 60 Gy didn't have a statistically significant influence in the multivariate analysis, although a total dose of more than 60 Gy was associated with improved survival in the univariate analysis. Concurrent chemotherapy was not associated with OS or LRFFS time in the univariate or multivariate analysis. A total of 74 patients (61.7%) experienced locoregional treatment failure. The most commonly documented acute toxicities were grade 1 and grade 2 toxicities in 61 patients (50.8%). There were 2 patients diagnosed with hypothyroidism as a late toxicity event. Conclusions: Definitive radiotherapy is a reasonable curative treatment option with laryngopharyngeal preservation for CESCC patients. Radical treatments for lymph node metastases may improve the OS and LRFFS times. Monitoring for thyroid function may be warranted during long-term follow-up.

Optimal radiotherapy dose in cervical esophageal squamous cell carcinoma patients treated with definitive concurrent chemoradiotherapy: A population based study.

BACKGROUND: The optimal radiotherapy dose for locally advanced cervical esophageal squamous cell carcinoma (C-ESqCC) treated with definitive concurrent chemoradiotherapy (dCCRT) is unclear. Here, we aimed to compare the survival of those treated with high dose versus standard dose via a population based approach. METHODS: Eligible C-ESqCC patients diagnosed between 2011 and 2017 were identified via the Taiwan Cancer Registry. We used propensity score (PS) weighting to balance observable potential confounders between groups. The hazard ratio (HR) of death and incidence of esophageal cancer mortality (IECM) were compared between high (60-70 Gy) and standard dose (50-50.4 Gy). We also evaluated the outcome in supplementary analyses via alternative approaches. RESULTS: Our primary analysis consisted of 141 patients in whom covariates were well balanced after PS weighting. The HR of death when high dose was compared with standard dose was 0.65 (95% confidence interval [CI]: 0.4-1.03, p = 0.07). The HR of IECM was 0.74 (p = 0.45). The HR of OS remained similarly insignificant in supplementary analyses. CONCLUSIONS: We observed a trend in favor of high radiotherapy dose versus standard dose for C-ESqCC treated with dCCRT in this population-based nonrandomized study. Further studies are needed to confirm the findings of the study.

Intensity-Modulated Radiotherapy versus Three-Dimensional Conformal Radiotherapy in Definitive Chemoradiotherapy for Cervical Esophageal Squamous Cell Carcinoma: Comparison of Survival Outcomes and Toxicities.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Intensity-modulated radiotherapy for cervical esophageal squamous cell carcinoma without hypopharyngeal invasion: dose distribution and clinical outcome.

Hypopharyngeal invasion would be a key finding in determining the extent of the irradiation fields in patients with cervical esophageal squamous cell carcinoma (CESCC). This study aimed to investigate the clinical outcomes of chemoradiotherapy using simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) omitting upper cervical lymph nodal irradiation in CESCC without hypopharyngeal invasion, and the dosimetric superiority of SIB-IMRT to 3D conformal radiotherapy (3DCRT). We retrospectively identified 21 CESCC patients without hypopharyngeal invasion [clinical Stage I/II/III/IV (M1LYM); 3/6/5/7] (UICC-TNM 7th edition) who underwent chemoradiotherapy using SIB-IMRT between 2009 and 2015. SIB-IMRT delivered 60 Gy to each primary tumor and the metastatic lymph nodes, and 48 Gy to elective lymph nodal regions, including Levels III and IV of the neck, supraclavicular, and upper mediastinal lymphatic regions, in 30 fractions. The overall survival rate, locoregional control rate, and initial recurrence site were evaluated. 3DCRT plans were created to perform dosimetric comparisons with SIB-IMRT. At a median follow-up of 64.5 months, the 5-year locoregional control and overall survival rates were 66.7% and 53.4%, respectively. Disease progressed in eight patients: all were locoregional progressions and no patients developed distant progression including upper cervical lymph nodal regions as initial recurrence sites. The planning study showed SIB-IMRT improved target coverage without compromising the dose to the organs at risk, compared with 3DCRT. In conclusion, omitting the elective nodal irradiation of the upper cervical lymph nodes was probably reasonable for CESCC patients without hypopharyngeal invasion. Locoregional progression remained the major progression site in this population.

Long-term impact of prognostic nutritional index in cervical esophageal squamous cell carcinoma patients undergoing definitive radiotherapy.

BACKGROUND: The prognostic nutritional index (PNI) has been found to have prognostic value in several cancers, and we aimed to determine its predictive value for the long-term prognosis of cervical esophageal squamous cell carcinoma (CESCC) patients treated with chemoradiotherapy (CRT). METHODS: The data for 106 CESCC patients who received radiotherapy with or without chemotherapy at the Cancer Hospital of Fujian Medical University from June 1, 2000 to December 31, 2015 were retrospectively analyzed. According to serum measurements taken before therapy, the PNI was calculated as albumin (g/L) + 5 × total lymphocyte count. The association between PNI and overall survival (OS) was determined by the Kaplan-Meier method and Cox proportional regression model analysis. RESULTS: The median follow-up time was 19 months. The optimal cutoff value for PNI was calculated to be 48.15, and patients were divided into a low PNI group (<48.15) and high PNI group (≥48.15). Univariate analysis showed that a low survival rate was significantly associated with male gender (P=0.004), tumor length ≥5.0 cm (P=0.043), radiotherapy technique (P=0.016), synchronous chemotherapy (P=0.012), lymphocyte-monocyte ratio (LMR) (P=0.007), neutrophil-lymphocyte ratio (NLR) (P=0.007), lung cancer inflammation index (ALI) (P=0.008), cervical esophageal carcinoma inflammation index (CEI) (P=0.043), and PNI (P<0.001). The OS was higher in the high PNI group than in the low PNI group. On multivariate analysis, gender (P=0.004), radiotherapy technique (P=0.029), and PNI (P=0.007) were independent prognostic factors in CESCC treated with CRT. CONCLUSIONS: The PNI value is a simple, reliable, and reproducible indicator for improving the accuracy of patient prognosis. And larger-scale studies are warranted to validate these findings.

Pattern of Failure in Surgically Treated Patients with Cervical Esophageal Squamous Cell Carcinoma.

OBJECTIVE: The aim of this study was to analyze the pattern of failure in patients who have undergone surgical resection for cervical esophageal squamous cell carcinoma. STUDY DESIGN: Case series with chart review. SETTING: University hospital. SUBJECTS AND METHODS: Sixty-two patients who had undergone surgical resection of cervical esophageal squamous cell carcinoma from January 2001 through April 2012. Sites of failure were documented. RESULTS: Twenty-nine patients had developed treatment failure. Of the 29 patients, 14, 13, and 14 had developed local failure, regional failure, and distant metastasis, respectively. Of the 13 regional failures, the images of 2 patients were lost. The other 11 regional failures included left lateral nodal disease at level II (n = 2), level III (n = 4), and level IV (n = 7); right lateral nodal disease at level II (n = 2), level III (n = 3), and level IV (n = 3); and level VI (n = 4). The overall 2-year local failure-free survival rate and regional failure-free survival rates were 79.6% and 58.6% (P = .04) for patients with stage II disease and 79.6% and 59.6% (P = .054) for patients with stage III disease, respectively. CONCLUSIONS: The pattern of failure of cervical esophageal squamous cell carcinoma is characterized by early locoregional failure, especially in patients with stage III disease.