N.R. Bennion

Automatic planning on hippocampal avoidance whole-brain radiotherapy

Mounting evidence suggests that radiation-induced damage to the hippocampus plays a role in neurocognitive decline for patients receiving whole-brain radiotherapy (WBRT). Hippocampal avoidance whole-brain radiotherapy (HA-WBRT) has been proposed to reduce the putative neurocognitive deficits by limiting the dose to the hippocampus. However, urgency of palliation for patients as well as the complexities of the treatment planning may be barriers to protocol enrollment to accumulate further clinical evidence. This warrants expedited quality planning of HA-WBRT. Pinnacle3 Automatic treatment planning was designed to increase planning efficiency while maintaining or improving plan quality and consistency. The aim of the present study is to evaluate the performance of the Pinnacle3 Auto-Planning on HA-WBRT treatment planning. Ten patients previously treated for brain metastases were selected. Hippocampal volumes were contoured on T1 magnetic resonance (MR) images, and planning target volumes (PTVs) were generated based on RTOG0933. The following 2 types of plans were generated by Pinnacle3 Auto-Planning: the one with 2 coplanar volumetric modulated arc therapy (VMAT) arcs and the other with 9-field noncoplanar intensity-modulated radiation therapy (IMRT). D2% and D98% of PTV were used to calculate homogeneity index (HI). HI and Paddick Conformity index (CI) of PTV as well as D100% and Dmax of the hippocampus were used to evaluate the plan quality. All the auto-plans met the dose coverage and constraint objectives based on RTOG0933. The auto-plans eliminated the necessity of generating pseudostructures by the planners, and it required little manual intervention which expedited the planning process. IMRT quality assurance (QA) results also suggest that all the auto-plans are practically acceptable on delivery. Pinnacle3 Auto-Planning generates acceptable plans by RTOG0933 criteria without time-consuming planning process. The expedited quality planning achieved by Auto-Planning (AP) may facilitate protocol enrollment of patients to further investigate the hippocampal-sparing effect and be used to ensure timely start of palliative treatment in future clinical practice.

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.

Estimation of internal organ motion-induced variance in radiation dose in non-gated radiotherapy

In the delivery of non-gated radiotherapy (RT), owing to intra-fraction organ motion, a certain degree of RT dose uncertainty is present. Herein, we propose a novel mathematical algorithm to estimate the mean and variance of RT dose that is delivered without gating. These parameters are specific to individual internal organ motion, dependent on individual treatment plans, and relevant to the RT delivery process. This algorithm uses images from a patients 4D simulation study to model the actual patient internal organ motion during RT delivery. All necessary dose rate calculations are performed in fixed patient internal organ motion states. The analytical and deterministic formulae of mean and variance in dose from non-gated RT were derived directly via statistical averaging of the calculated dose rate over possible random internal organ motion initial phases, and did not require constructing relevant histograms. All results are expressed in dose rate Fourier transform coefficients for computational efficiency. Exact solutions are provided to simplified, yet still clinically relevant, cases. Results from a volumetric-modulated arc therapy (VMAT) patient case are also presented. The results obtained from our mathematical algorithm can aid clinical decisions by providing information regarding both mean and variance of radiation dose to non-gated patients prior to RT delivery.

Chemoradiotherapy for locally advanced squamous cell carcinoma of the oropharynx: Does completion of systemic therapy affect outcomes?

INTRODUCTION Current standard of care for locally advanced squamous cell carcinoma of the oropharynx (LA-OPC) consists of concurrent chemoradiotherapy. Due to toxicities associated with this treatment, a significant portion of patients are unable to complete the systemic therapy portion of their treatment course. The impact of incomplete systemic therapy on patient outcomes remains unclear. METHODS Demographic, treatment, and outcome data were retrospectively collected for patients with LA-OPC treated definitively with concurrent chemoradiotherapy between 2007 and 2014. Overall and disease-free survivals were estimated via the Kaplan Meier method. Log rank test was used to compare distributions of survival amongst groups. Cox regression was utilized for all multivariate analyses. P values of <0.05 were considered statistically significant. RESULTS In total, 73 patients with LA-OPC were identified with a median follow-up of 3.4years. Concurrent systemic therapy regimens consisted of bolus cisplatin every 3weeks (76.7%), weekly cetuximab (20.5%) and weekly cisplatin (2.7%). Forty-three patients (58.9%) were able to complete the prescribed concurrent systemic regimens. Upon multivariate analyses, patients who did not complete systemic therapy were noted to have a non-significant trend towards increased distant failure (20.0% vs 7.0%, p=0.12). Additionally, patients who did not complete systemic therapy were noted to have a near significant trend towards increased risk of death (36.7% vs 17.9%, p=0.053). CONCLUSIONS These results suggest that completing systemic therapy may affect survival in patients undergoing definitive radiotherapy with concurrent systemic therapy for LA-OPC. Further, this data demonstrates that though local recurrences are not affected when planned systemic therapy cycles are omitted, the risk of distant failure may increase. These associations require further study to clarify the effect Incomplete systemic therapy has on outcomes for LA-OPC.

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.

Osteosarcoma of the larynx: treatment outcomes and patterns of failure analysis

The incidence of laryngeal sarcoma is exceedingly low with osteosarcomas of the larynx being rarer still, comprising less than 1% of all associated malignancies. To date, only 32 cases have been reported since this pathologic entity was first described in 1942. In this article, we discuss the most recent case of laryngeal osteosarcoma in a patient presenting with respiratory distress found to be due to a tumor mass arising from her cricoid cartilage. We further summarize current knowledge regarding the epidemiology, presentation, and diagnosis of this uncommon disease. Lastly, we synthesize all available information regarding treatment and outcomes of the 32 previously described cases of osteosarcoma of the larynx as well as the presently described case in an attempt to offer some insight regarding optimal treatment in future cases.

Fractionated stereotactic radiation therapy for vestibular schwannomas: Dosimetric factors predictive of hearing outcomes

PURPOSE To determine dosimetric factors predictive of hearing loss in vestibular schwannoma (VS) patients treated with definitive fractionated stereotactic radiation therapy (FSRT), and to report tumor control, serviceable hearing preservation, and cranial nerve toxicities. METHODS AND MATERIALS We identified 45 patients (29 men and 16 women) with unilateral sporadic VS, who underwent definitive FSRT. All patients had serviceable hearing prior to treatment, defined as Gardner-Robertson Class 1 or 2. All patients underwent an audiogram before the start of treatment and serial audiometric assessments after treatment. The median audiometric follow-up time was 35.2 months (range, 5.0-89.7 months). Patients underwent a median of 4.5 (range, 1-9) posttreatment audiograms. The ipsilateral cochlea was contoured retrospectively, and dosimetric data were used to determine factors predictive of losing serviceable hearing. The median clinical follow-up time was 29.9 months (range, 1.5-83.6 months). RESULTS At the time of the last audiometric follow-up, 62% of patients retained serviceable hearing. The actuarial 1-, 2-, and 3-year serviceable hearing preservation rates were 83%, 75%, and 51%, respectively. The estimated median time to loss of serviceable hearing was 42.2 months. On multivariate analysis, cochlear volume <0.15 mL (hazard ratio, 2.849; 95% confidence interval, 1.116-7.270; P = .029) and mean cochlear dose <4000 cGy (hazard ratio, 3.178; 95% confidence interval, 1.116-9.049; P = .030) were statistically significant variables associated with serviceable hearing preservation. The actuarial tumor control was 100%. Three of 39 patients (8%) developed hemifacial spasm after FSRT (House-Brackmann Grade 3), 2 of which completely resolved. No patients experienced deterioration in trigeminal nerve function after FSRT. CONCLUSIONS Fractionated stereotactic radiation therapy can provide excellent tumor control with acceptable clinical outcomes. The mean dose to the cochlea is highly predictive of the probability of maintaining serviceable hearing after FSRT.

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.