Abhijeet R. Bhirud

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.

A Review of the Impact of Preoperative Chemoradiotherapy on Outcome and Postoperative Complications in Esophageal Cancer Patients

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.

Dosimetric parameters correlate with duodenal histopathologic damage after stereotactic body radiotherapy for pancreatic cancer: Secondary analysis of a prospective clinical trial

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 5-8Gy) 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 the Clinical Terminology Criteria for Adverse Events (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 37Gy. Median duodenal V5-V40 were 64, 62, 52, 39, 27, 14, 5 and 0cc, 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.

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.

Target migration from re-inflation of adjacent atelectasis during lung stereotactic body radiotherapy

Stereotactic body radiotherapy (SBRT) is a widely accepted option for the treatment of medically inoperable early-stage non-small cell lung cancer (NSCLC). Herein, we highlight the importance of interfraction image guidance during SBRT. We describe a case of early-stage NSCLC associated with segmental atelectasis that translocated 15 mm anteroinferiorly due to re-expansion of the adjacent segmental atelectasis following the first fraction. The case exemplifies the importance of cross-sectional image-guided radiotherapy that shows the intended target, as opposed to aligning based on rigid anatomy alone, especially in cases associated with potentially “volatile” anatomic areas.

Which Prognostic Index Is Most Appropriate in the Setting of Delayed Stereotactic Radiosurgery for Brain Metastases

Objectives To determine if five commonly used prognostic indices (PIs) – recursive partitioning analysis (RPA), Score Index for Radiosurgery (SIR), Basic Score for Brain Metastases (BSBM), graded prognostic assessment (GPA), and the diagnosis-specific GPA – are valid following delay between diagnosis and treatment of brain metastases. Methods In a single-institutional cohort, records of patients who underwent stereotactic radiosurgery (SRS) more than 30 days from diagnosis of brain metastases were collected, and five PI scores were calculated for each patient. For each PI, three score-based groupings were made to examine survival differences by means of adjusted log-rank analysis and area under the curve (AUC). Results Of 121 patients with sufficient PI information, 72 underwent SRS more than 30 days after diagnosis. Median age and Karnofsky performance status were 60 years and 80, respectively. Forty-three (60%) patients had lung primaries. Prior to SRS, 38 (52.8%) and 12 (16.7%) patients underwent whole brain radiation therapy (WBRT) and surgery, respectively. Two (2.8%) patients underwent both WBRT and surgery prior to SRS. A median of two lesions were treated per SRS course. Median survival of the cohort was 9.0 months. Using adjusted log-rank analysis for pairwise comparison, BSBM and GPA showed significance between two out of the three prognostic groups, while the other scores showed either one or no significant differences on comparison. AUC demonstrated good applicability for BSBM, RPA, and GPA, although SIR was statistically less prognostic than the other PIs. Conclusion The PIs analyzed in this study were applicable in the setting of delayed SRS. Although these data are hypothesis generating, they serve to encourage further analyses to validate a PI that is most optimal for these patients.

Comparison of outcomes between rectal squamous cell carcinoma and adenocarcinoma

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.

EP-1281: DVH relationships in rectal cancer: effects of contouring methods and patient positioning

ESTRO 35 2016 _____________________________________________________________________________________________________ years actuarial local control (LC) rates were 100% and 88%, respectively. Median overall survival (OS) was 24 months. Actuarial OS rates at 1 and 2 years were 83% and 38%, respectively. Median progression-free survival (PFS) was 7 months. No patients experienced radiation-induced liver disease (RILD) or grade >3 toxicity.

Patterns of radiotherapy and its impact on survival in patients with locally advanced gastric and gastroesophageal junction adenocarcinoma: Before and after the publication of the MAGIC trial.

125 Background: The intergroup 0116 trial for locally advanced gastric (GA) and gastroesophageal junction adenocarcinoma (GEJA) established postoperative chemoradiation therapy as the standard of care. However, since the publication of the MAGIC trial in 2006, some physicians prefer perioperative chemotherapy rather than postoperative chemoradiation. The goal of this study is to examine the use of radiotherapy (RT) and its impact on survival in patients diagnosed 3 years prior to and after the publication of the MAGIC trial. Methods: Patients with stage T2-4 or N+ and M0 GA (3339) or GEJA (1868) diagnosed between 2004 and 2009 who have had a primary tumor resection with at least 3 years of follow up were identified from the SEER database. Regression models were used to analyze factors influencing the use of RT and its effect on survival. Kaplan Meier plots and log-rank tests were used for survival comparisons. Results: From 2004 to 2009, there was no change in the ratio of RT/no RT. About 33% of patients ...

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.