Metachronous medulloblastoma and glioblastoma: Implications for clinical and technical aspects of re-irradiation.

A seven-year-old male underwent surgical resection and chemoradiation for average risk medulloblastoma; twelve years later, the presence of a necrotic and infiltrative mass in the same area and invading the brainstem prompted a subtotal resection. Pathology was indicative of glioblastoma. He was then treated with concurrent temozolomide and using biologically effective dose calculations for gross residual tumor tissue in the brainstem as well as brainstem tolerance, a radiotherapy dose of 3750 cGy was chosen, fractionated in twice-daily fractions of 125 cGy each. The gross tumor volume was expanded with a 5 mm margin to the planning target volume, which was also judiciously subtracted from the normal brainstem. He completed his radiotherapy course with subsequent imaging free of residual tumor and continued adjuvant temozolomide and remains under follow-up surveillance. This case underscores the rarity of metachronous medulloblastoma and glioblastoma, of which only five known cases heretofore have been described. We discuss the technicalities of radiotherapy planning in this patient, including common hurdles for radiation oncologists in similar patients.

Atypical teratoid rhabdoid tumor: long-term survival after chemoradiotherapy.

PURPOSE: Atypical teratoid rhabdoid tumors (ATRTs) arise from the central nervous system largely in the pediatric population. They portend a very poor prognosis with few long-term survivors. We describe a series of five cases at our institution. METHODS: We conducted a retrospective chart review and clinical follow-up. RESULTS: Three patients underwent chemoradiation after surgical resection; the two patients whose caretakers declined this therapy passed away soon after diagnosis. Chemoradiation included intravenous and intrathecal chemotherapy as well as intensity-modulated radiotherapy after resection. Of the patients receiving chemoradiation, two patients had infratentorial tumors, two had gross residual tumor after resection, and two were under the age of 3 years. The three patients receiving trimodality therapy remain clinically and symptomatically disease-free with follow-up times of 44, 46, and 55 months. Two of the patients have mild neuropsychiatric sequelae after therapy. CONCLUSIONS: Long-term, high-volume trials of ATRT are currently not published. We offer experience in successful long-term survival of this tumor treated with chemoradiotherapy.

Quantification of renal function following stereotactic body radiotherapy for pancreatic cancer: secondary dosimetric analysis of a prospective clinical trial.

BACKGROUND: This is the first known study examining renal function following stereotactic body radiotherapy (SBRT) for pancreatic head adenocarcinoma. METHODS: Thirty-eight borderline-resectable/unresectable patients, part of an ongoing prospective trial, underwent 3 cycles of gemcitabine/5-fluorouracil followed by SBRT (5 daily fractions of 5/6/7/8 Gy) and concurrent nelfinavir. Thereafter, in resectable cases, surgery was performed within 4-8 weeks. The last available pre-SBRT creatinine was recorded, along with the highest post-SBRT value. Glomerular filtration rate (GFR) was calculated by the commonly-utilized Modification of Diet in Renal Disease formula. GFR decline was defined as the post-SBRT nadir GFR minus the pre-SBRT GFR. Correlations with the V5-V30, and mean/maximum kidney doses was performed. Statistics included Pearson correlation, Mann-Whitney, and Fisher's exact tests. RESULTS: The median total kidney volume was 355 cm3. Median dosimetric values were as follows: V5 (209 cm3), V10 (103 cm3), V15 (9 cm3), V20 (0 cm3), V25 (0 cm3); and mean (6.7 Gy) & maximum kidney dose (18.3 Gy). Median GFR change was -23 (range, -105 to 25) mL/min/1.73 cm2. Of all dosimetric parameters, only V5 was significantly associated with changes in GFR (Pearson r = -0.40, p = 0.012). In patients with V5 < 210 cm3, median GFR change was -11.8 mL/min/1.73 cm2, as compared with -37.1 mL/min/1.73 cm2 change in those with V5 ≥ 210 cm3 (p = 0.02). A GFR change < -23 mL/min/1.73 cm2 was observed in 6/20 (30%) patients with V5 < 210 cm3, versus 15/18 (83%) of those with V5 ≥ 210 cm3. Patients with V5 ≥ 210 cm3 were over ten times as likely to have GFR change < -23 mL/min/1.73 cm2 (p = 0.003). Using linear regression, GFR change ≈ -0.1748 × V5(cm3) + 8.63. CONCLUSIONS: In the first known analysis of renal function after pancreatic SBRT, evaluating patients on a prospective study, V5 ≥ 210 cm3 was associated with a post-SBRT GFR decline of >23 mL/min/1.73 cm2. If V5 is kept <210 cm3, median GFR decline was only 11.8 mL/min/1.73 cm2. Further validation is needed to ascertain definite dose-volume parameters and examine late renal decline.

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.

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.

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.

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.

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.

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.