ObjectiveRadiation therapy (RT) for esophageal cancer often results in unintended radiation doses delivered to the heart owing to anatomic proximity. Using the Surveillance, Epidemiology, and End Results (SEER) database, we examined late cardiac death in survivors of esophageal cancer that had or had not received RT.Methods5,630 patients were identified that were diagnosed with esophageal squamous cell carcinoma (SCC) or adenocarcinoma (AC) from 1973–2012, who were followed for at least 5 years after therapy. Examined risk factors for cardiac death included age (≤55/56-65/66-75/>75), gender, race (white/non-white), stage (local/regional/distant), histology (SCC/AC), esophageal location (<18cm/18-24cm/25-32cm/33-40cm from incisors), diagnosis year (1973-1992/1993-2002/2003-2012), and receipt of surgery and/or RT. Time to cardiac death was evaluated using the Kaplan-Meier method. A Cox model was used to evaluate risk factors for cardiac death in propensity score matched data.ResultsPatients who received RT were younger, diagnosed more recently, had more advanced disease, SCC histology, and no surgery. The RT group had higher risk of cardiac death than the no-RT group (log-rank p<0.0001). The median time to cardiac death in the RT group was 289 months (95% CI, 255–367) and was not reached in the no-RT group. The probability of cardiac death increased with age and decreased with diagnosis year, and this trend was more pronounced in the RT group. Multivariate analysis found RT to be associated with higher probability of cardiac death (OR 1.23, 95% CI 1.03–1.47, HR 1.961, 95% CI 1.466–2.624). Lower esophageal subsite (33–40 cm) was also associated with a higher risk of cardiac death. Other variables were not associated with cardiac death.ConclusionsRecognizing the limitations of a SEER analysis including lack of comorbidity accountability, these data should prompt more definitive study as to whether a possible associative effect of RT on cardiac death could potentially be a causative effect.

Large, population‐based analyses of rectal squamous cell carcinoma (SCC) have not been previously conducted. We assessed patterns of care, prognostic factors, and outcomes of rectal SCC and adenocarcinoma (AC) in population‐based cohorts. Surveillance, Epidemiology, and End Results (SEER) registry searches were performed (1998–2011), producing 42,308 nonmetastatic rectal cancer patients (999 SCC and 41,309 AC). Patient, tumor, and treatment characteristics were compared. Based on risk factors, SCC/AC groups were subdivided into low‐, intermediate‐, and high‐risk groups. Overall survival (OS) was compared between histological and risk groups using Kaplan–Meier method and log‐rank test. Multivariate logistic regression models evaluated prognostic factors for 5‐year survival. Cox regression modeling was performed on propensity‐matched data. Rectal SCC, more common in females and associated with larger tumors of higher grade, was more often treated with radiotherapy (RT) than surgery. Surgery was associated with higher OS in AC but not SCC, and RT had proportionally greater benefits in SCC. These effects of RT and surgery were retained when stratified into risk groups (particularly high/intermediate‐risk). Favorable prognostic factors for survival included younger age, non‐black race, SCC histology, size ≤3.9 cm, localized stage, lower grade, surgery, and RT. For SCC, race, tumor grade, and surgery were not prognostic factors for survival. Cox regression modeling of propensity‐matched data showed that AC histology increased risk of death versus SCC. In the largest analysis of rectal SCC to date, and in the notable absence (and unlikelihood) of prospective data, nonsurgical and RT‐based treatment is recommended.

Preoperative chemoradiotherapy has emerged in the treatment of esophageal cancer as a means to down-stage tumors, improve local control, and possibly improve overall survival. However, there are concerns that postoperative complications may be increased by preoperative chemoradiotherapy. We review the rationale for preoperative chemoradiotherapy. We review the literature to identify the potential postoperative complications, the risk of complications, and the risk factors for complications. Although individual and previous studies have shown an increased risk of postoperative complications, the 4 most recent randomized trials published after the year 2000 have not shown an increase in postoperative complications and mortality rates in patients treated with preoperative chemoradiation compared with patients treated with surgery alone. Pulmonary complications are frequently reported, and we focus on dosimetric factors that can be used to minimize lung toxicity. Several dose-volume-histogram parameters, including V10≥40%, V15≥30%, V20≥20%, have been shown to correlate with 32% to 35% of pulmonary complications including pneumonia and acute respiratory distress syndrome. More recent evidence has suggested that an absolute volume of lung spared doses of > 5 Gy (VS5) correlates with pulmonary complications. As these data show, low-dose volume may be more important in the prevention of pulmonary complications than high-dose volume. These dosimetric constraints can be used by physicians to prevent postoperative pulmonary complications in patients treated with preoperative chemoradiotherapy.

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Purpose Prospectively assess relationships between dosimetric parameters and histopathologic/clinical duodenal toxicities in patients on a phase I trial for pancreatic cancer. Methods Forty-six borderline resectable/unresectable patients were enrolled on a prospective trial testing neoadjuvant gemcitabine/5-fluorouracil followed by SBRT (5 daily fractions of 5–8 Gy) and concurrent nelfinavir. Post-SBRT surgery was performed in 13 resectable patients, which constituted the patient population herein. Pathologic duodenal damage was assessed using predetermined criteria: 1, no/minimal; 2, moderate; and 3, marked damage. Clinical toxicities were assessed per CTCAE. Duodenal dosimetric parameters included V5–V40 and mean/maximum doses. Spearman correlation and linear regression evaluated associations between dosimetric parameters and clinical/pathologic duodenal toxicity. Results The median duodenal mean and maximum doses were 20 and 37 Gy. Median duodenal V5–V40 were 64, 62, 52, 39, 27, 14, 5 and 0 cc, respectively. The median duodenal damage score was 2 (four 1, eight 2, and one 3). Higher duodenal damage scores correlated with higher duodenal mean doses (r = 0.75, p = 0.003), V35 (r = 0.61, p = 0.03), V30 (r =0.67, p = 0.01), V25 (r =0.68, p = 0.01), V20 (r = 0.56, p = 0.05), and the planning target volume (PTV) mean (r =0.59, p = 0.03) and maximum (r = 0.61, p = 0.03) doses. Clinical toxicities did not correlate with dosimetric parameters or duodenal pathologic damage. Conclusions Duodenal histologic damage correlates with mean duodenal dose, V20–V35, and PTV mean/−maximum doses.