Kyle A. Denniston

Radiation Therapy and Cardiac Death in Long-Term Survivors of Esophageal Cancer: An Analysis of the Surveillance, Epidemiology, and End Result Database.

Objective Radiation 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. Methods 5,630 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. Results Patients 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. Conclusions Recognizing 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.

Evaluation of the Dosimetric Feasibility of Hippocampal Sparing Intensity-Modulated Radiotherapy in Patients with Locally Advanced Nasopharyngeal Carcinoma

Purpose The objective of this study was to evaluate the dosimetric feasibility of using hippocampus (HPC) sparing intensity-modulated radiotherapy (IMRT) in patients with locally advanced nasopharyngeal carcinoma (NPC). Materials/Methods Eight cases of either T3 or T4 NPC were selected for this study. Standard IMRT treatment plans were constructed using the volume and dose constraints for the targets and organs at risk (OAR) per Radiation Therapy Oncology Group (RTOG) 0615 protocol. Experimental plans were constructed using the same criteria, with the addition of the HPC as an OAR. The two dose-volume histograms for each case were compared for the targets and OARs. Results All plans achieved the protocol dose criteria. The homogeneity index, conformity index, and coverage index for the planning target volumes (PTVs) were not significantly compromised by the avoidance of the HPC. The doses to all OARs, excluding the HPC, were similar. Both the dose (Dmax, D2%, D40%, Dmean, Dmedian, D98% and Dmin) and volume (V5, V10, V15, V20, V30, V40 and V50) parameters for the HPC were significantly lower in the HPC sparing plans (p<0.05), except for Dmin (P = 0.06) and V5 (P = 0.12). Conclusions IMRT for patients with locally advanced NPC exposes the HPC to a significant radiation dose. HPC sparing IMRT planning significantly decreases this dose, with minimal impact on the therapeutic targets and other OARs.

A Comparison of Pediatric vs. Adult Patients with the Ewing Sarcoma Family of Tumors

Purpose This study sought to identify differences in clinical characteristics, outcomes, and treatments between adult and pediatric patients with the Ewing sarcoma family of tumors (ESFT). Methods By using the Surveillance, Epidemiology, and End Results database from 1983 to 2013, 1,870 patients were analyzed (n = 976 pediatric, n = 894 adult). Between the two groups, demographic, tumor, and treatment characteristics were collated and compared. The chi-square test determined differences in proportions of the variables between groups. Survival analysis was performed using the Kaplan–Meier method; distributions were compared using the log-rank test. Univariate and multivariate analyses were performed to examine variables correlating with overall survival (OS), the primary endpoint. Results Adult patients had a poorer prognosis and were more likely to present with primitive neuroectodermal tumor (PNET) histology, along with distant metastasis and soft tissue primary site. In patients undergoing surgery, radiation therapy (RT) was not associated with higher OS in either children or adults. If no surgery was performed, receipt of RT was associated with higher OS in adults but not children. Adulthood negatively correlated with OS on multivariate analysis when adjusting for potential confounding factors. Other salient factors associated with OS were male gender, metastatic disease, non-extremity bone location, treatment era, and PNET histology. However, when examining the most recent subset (patients treated from 2004 to 2013), RT was associated with improved OS in both pediatrics and adults, which was an independent predictor on multivariate analysis. Conclusion Adult patients with ESFT have inferior survival compared to pediatric patients, likely related to earlier clinical detection in the latter.

A comparison of clinical and radiologic outcomes between frame-based and frameless stereotactic radiosurgery for brain metastases

PURPOSE Modern experiences in stereotactic radiosurgery (SRS) report noninvasive frameless techniques as an effective alternative to frame-based SRS. Frameless techniques potentially increase positional uncertainty and planning target volume margins are frequently used. Here, we compare rates of local control and radiation necrosis in frameless versus frame-based SRS. METHODS AND MATERIALS Ninety-eight patients (170 lesions) with radiologic and clinical follow-up were analyzed. Group 1 contained 34 patients (61 lesions) immobilized with an invasive stereotactic frame. Group 2 had 64 patients (109 lesions) immobilized with a frameless SRS mask. Patient, tumor, and treatment characteristics were recorded, as were intervals to local recurrence and radiation necrosis (asymptomatic and symptomatic). RESULTS Median patient age was 59 years (range, 25-89), and Karnofsky performance scale was 80 (range, 50-100). Median radiologic and clinical follow-up was 6.5 months (range, 0.7-44.3) and 7 months (range, 0.7-45.7). A median of 2 tumors were treated per course (range, 1-5) with a median dose of 18 Gy (range, 13-24 Gy). The median time to local failure was not reached, and Kaplan-Meier estimates of local failure were not statistically significant between groups (P = .303). Actuarial 6-month local failure rates were 7.2% in group 1 and 12.6% in group 2 (P = .295), with 12-month local failure rates of 14.5% and 26.8% (P = .185), respectively. There was no statistically significant difference in symptomatic (P = .391) or asymptomatic (P = .149) radiation necrosis. Six-month radiation necrosis was 0% in group 1 and 1.6% in group 2 (P = .311) with 12-month rates of 20.2% and 3.8%, respectively (P = .059). Median time to necrosis was not reached in group 1, but was 44 months in group 2. CONCLUSIONS Frameless SRS demonstrates clinical outcomes comparable to frame-based techniques with respect to local failure and radiation necrosis.

Effect of Akimbo versus Raised Arm Positioning on Breast and Cardiopulmonary Dosimetry in Pediatric Hodgkin Lymphoma.

Purpose In pediatric Hodgkin lymphoma (HL), radiotherapy (RT)-related late toxicities are a prime concern during treatment planning. This is the first study to examine whether arm positioning (raised versus akimbo) result in differential cardiopulmonary and breast doses in patients undergoing mediastinal RT. Methods Two treatment plans were made for each patient (akimbo/arms raised); treatment was per Children’s Oncology Group AHOD0031 protocol, including AP/PA fields. The anterior midline T6–T7 disk space was used as an anatomic reference of “midline.” Heart/lungs were contoured for each setup. For females, breasts were also contoured and nipple positions identified. Volumetric centers of contoured organs were defined and three-dimensional distances from “midline” were computed. Analyzed dosimetric parameters included V5 (volume receiving ≥5 Gy), V10, V15, V20, and mean dose. Statistics were performed using the Mann–Whitney test. Results Fifteen (6 females, 9 males) pediatric HL patients treated with mediastinal RT were analyzed. The median lateral distance from the breast center/nipple to “midline” with arms akimbo was larger than that with arms raised (8.6 vs. 7.7 cm left breast, p = 0.04; 10.7 vs. 9.2 cm left nipple, p = 0.04; 8.7 vs. 7.0 cm right breast, p = 0.004; 9.9 vs. 7.9 cm right nipple, p = 0.007). Raised arm position was associated with a median 2.8/3.0 cm decrease in breast/nipple separation, respectively. There were no significant differences in craniocaudal breast/nipple position based on arm positioning (p > 0.05). Increasing breast volume was correlated with larger arm position-related changes in breast/nipple separation (r = 0.74, p = 0.06/r = 0.85, p = 0.02). Akimbo positioning lowered median breast V5, V10, V15, and mean dose (p < 0.05), with no differences observed in patients with both mediastinal and axillary disease for any parameters (p > 0.05). Arm position had no significant effect on cardiopulmonary doses. Conclusion Akimbo arm positioning may be advantageous to decrease breast doses in female pediatric HL patients undergoing mediastinal RT, especially in the absence of axillary disease.