Small Cell Carcinoma of the Esophagus: A Nationwide Analysis of Treatment and Outcome at Patient Level in Locoregional Disease.

BACKGROUND AND PURPOSE: Small cell carcinoma of the esophagus (SCEC) is a rare subtype of esophageal cancer for which optimal treatment is unknown. We analyzed the impact of treatment factors on outcome in patients with nonmetastasized SCEC. METHODS: Patients with a histologically confirmed SCEC without distant metastases were analyzed in a nationwide multicenter retrospective cohort. All patients received radiotherapy as part of curative treatment between January 2000 and December 2014. Details on treatment and outcome were retrieved from individual charts. Cox regression analysis was used to determine prognostic factors for survival. RESULTS: Fifty-eight patients were analyzed. Median survival was 16 months (95% confidence interval, 11-21 mo). Infield recurrences occurred in 25%, distant metastases in 45%, and brain metastases in 12%. In total, 63% of patients developed a recurrence. Most recurrences (67%) occurred within 1 year. In univariable analyses an increased number of chemotherapy cycles (>3) and lower radiotherapy doses (<45 Gy) were associated with improved survival. T-stage, N-stage, treatment period, type of chemotherapy, prophylactic cranial irradiation, and age were not associated with survival. In multivariable analyses, only the number of chemotherapy cycles was associated with better survival (hazard ratio, 0.78; P=0.006). CONCLUSIONS: SCEC recurs frequently at distant sites after definitive chemoradiotherapy and usually within 1 year after curative treatment. With a dose of 45 to 50 Gy, infield recurrence rate was low. We found a relationship between number of received chemotherapy cycles and survival with best results obtained after at least 4 cycles of chemotherapy.

Predictive parameters of symptomatic radiation pneumonitis following stereotactic or hypofractionated radiotherapy delivered using volumetric modulated arcs.

PURPOSE: To identify dosimetric factors that predict development of radiation pneumonitis (RP) following stereotactic or hypofractionated radiotherapy for lung tumors. METHODS: Seventy-nine consecutive patients with either a planning target volume (PTV)>100 cm(3) (n=69) or prior pneumonectomy or bi-lobectomy (n=13) were identified. Radiation doses (range: 5-50 Gy, with 5 Gy increments) were converted to equivalent doses (EQD(2 Gy)) (α/ß=3). Total lung (TL), ipsilateral (IL) and contralateral lung (CL) volumes minus PTV, receiving 5 Gy (V5) up to 50 Gy (V50) and mean lung dose (MLD) were analyzed. Predictors of grade ≥3 RP (CTCAEv4.03) were identified with concordance-statistics (C-statistic) and p-values used to quantify the performance of the model. Factors found to be significant were entered into a recursive partitioning analysis (RPA). RESULTS: Median PTV was 150 cm(3). Grade ≥3 RP was observed in 8 patients (10%). In univariable analysis, CL-MLD, CL-V5-15, TL-MLD, TL-V5-V10 and ITV size were predictive of RP (p<0.05). In multivariable analysis, contralateral MLD (p=.007) and ITV (p=.063) were the strongest predictors of grade ≥3 RP, with excellent discrimination (C-statistic: 0.868). CONCLUSION: Contralateral MLD and ITV size are both strong predictors of grade ≥3 RP post treatment. Planning constraints should aim to keep contralateral MLD below 3.6 Gy.

Incidence and risk factors for chest wall toxicity after risk-adapted stereotactic radiotherapy for early-stage lung cancer.

INTRODUCTION: High local control rates are reported after stereotactic ablative body radiotherapy (SABR) in stage I non-small cell lung cancer. Toxicity is uncommon, but few reports on long-term follow-up are available. We studied the incidence of chest wall pain (CWP) and rib fractures in patients with long-term follow-up. METHODS: Between 2003 and 2009, 500 patients (530 tumors) underwent SABR using risk-adapted fractionation schemes, consisting of three fractions of 20 Gy, five fractions of 12 Gy, or eight fractions of 7.5 Gy. Toxicity data were collected in a prospective database and scored using Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Chest wall volumes receiving doses of 30, 40, 45, and 50 Gy (V30 Gy-V50 Gy) and maximum dose in 2 cm of chest wall (D2 ml) were determined for patients with CWP or rib fractures (n = 57). RESULTS: With a median follow-up of 33 months, the 3-year overall survival and local control rates were 53.1% and 90.4%, respectively. CWP developed in 11.4% of patients and was severe (grade 3) in 2.0%. Rib fractures were observed in eight patients (1.6%), accompanied by CWP in seven of these patients. On multivariate analysis, patients with CWP had larger treatment volumes and shorter tumor-chest wall distances, whereas patients with rib fractures had larger tumor diameters and treatment volumes. Grade 3 CWP and rib fractures were associated with larger volumes of chest wall receiving doses of 30 to 50 Gy and rib fractures specifically with a higher maximum dose in the chest wall. CONCLUSIONS: Severe (grade 3) chest wall toxicity is uncommon after risk-adapted SABR and manifests in 2% or fewer of patients.