Phase 1 Randomized Trial of Stereotactic Body Radiation Therapy Followed by Nivolumab plus Ipilimumab or Nivolumab Alone in Advanced/Unresectable Hepatocellular Carcinoma.

PURPOSE: Immunotherapy has emerged as a promising therapeutic option for advanced or unresectable hepatocellular carcinoma (HCC). However, survival remains poor with only a subset of patients deriving benefit. This trial investigated the safety and efficacy of stereotactic body radiation therapy (SBRT) with immunotherapy in HCC. METHODS AND MATERIALS: In this multicenter phase 1 randomized trial, patients with advanced or unresectable HCC received liver SBRT (40 Gy in 5 fractions) followed by either nivolumab alone or nivolumab plus ipilimumab. The primary endpoint was dose-limiting toxicity occurring within 6 months of SBRT. Secondary endpoints included overall response rate, progression-free survival, overall survival (OS), distant disease control, and local control of the irradiated tumor. Disease status and response endpoints were assessed radiographically every 8 weeks until progression or initiation of nonprotocol therapy. Response was determined using both RECIST (Response Evaluation Criteria in Solid Tumors) 1.1 and iRECIST. RESULTS: Fourteen patients were enrolled across 3 centers. Thirteen patients were evaluated for study endpoints. The study was closed early because of slow accrual. The median follow-up time was 42.7 months. Dose-limiting toxicities within 6 months occurred in 2 (15.4%) of 13 patients: 1 of 6 patients in the nivolumab arm (16.7%; 90% confidence interval [CI], 0.9%-58.2%) and 1 of 7 patients in the nivolumab plus ipilimumab arm (14.3%; 90% CI, 0.7%-52.1%). Grade 3 adverse events occurred in 8 (61.6%), 5 (71.4%), and 3 (50.0%) patients in the overall nivolumab plus ipilimumab and nivolumab cohorts. Grade 3 hepatotoxicity occurred in 4 (30.8%), 3 (42.9%), and 1 (16.7%) patients in the respective cohorts. Clinical outcomes favored the nivolumab plus ipilimumab arm compared with nivolumab alone, including an overall response rate of 57% (4 of 7 patients; 90% CI, 23%-87%) versus 0% (0 of 6 patients; 90% CI, 0%-39%), median progression-free survival of 11.6 months (90% CI, 4.5 months to not reached) versus 2.7 months (90% CI, 1.3-4.7 months), and median OS of 41.6 months (90% CI, 4.5 months to not reached) versus 4.7 months (90% CI, 2.0-16.2 months) (all P < .05). With combination immunotherapy, 3-year OS was 57% (90% CI, 23%-81%), with 2 patients alive after 42.7 months without progression and negative PET. CONCLUSIONS: In this first prospective trial investigating the combination of SBRT and immunotherapy for HCC, multimodal therapy demonstrated acceptable safety. SBRT with nivolumab plus ipilimumab compared favorably to outcomes of immunotherapy alone and warrants further investigation.

Retreatment of Recurrent or Second Primary Head and Neck Cancer After Prior Radiation: Executive Summary of the American Radium Society Appropriate Use Criteria.

Retreatment of recurrent or second primary head and neck cancers occurring in a previously irradiated field is complex. Few guidelines exist to support practice. We performed an updated literature search of peer-reviewed journals in a systematic fashion. Search terms, key questions, and associated clinical case variants were formed by panel consensus. The literature search informed the committee during a blinded vote on the appropriateness of treatment options via the modified Delphi method. The final number of citations retained for review was 274. These informed 5 key questions, which focused on patient selection, adjuvant reirradiation, definitive reirradiation, stereotactic body radiation, and reirradiation to treat nonsquamous cancer. Results of the consensus voting are presented along with discussion of the most current evidence. This provides updated evidence-based recommendations and guidelines for the retreatment of recurrent or second primary cancer of the head and neck.

Palliative radiation for bone metastases from hepatocellular carcinoma: practice patterns and the amount of remaining life spent receiving treatment.

BACKGROUND: Palliative radiation therapy (RT) for bone metastases (BMs) is a common practice. Wide variation exists in clinically used dose schema despite numerous studies demonstrating palliative equipoise between single and multifraction courses. We hypothesize that fraction scheme for palliating BMs for hepatocellular carcinoma (HCC) significantly affects how patients spend their remaining time. METHODS: Patients with osseous HCC metastases who received RT were identified from the National Cancer Database [2004-2013]. The percentage of remaining life spent receiving radiation therapy (PRLSRT) and the number of incomplete RT courses were calculated. Kaplan-Meier analysis and Cox proportional hazards models were used to evaluate trends and predictors. RESULTS: A total of 1,331 patients met the inclusion criteria. Median overall survival (OS) was 3.3 months. Just 49 (3.7%) of patients received single fraction RT and 34% received >10 fractions. The mean and median PRLSRT were as follows: 1 fraction (8.9% and 3.0%), 2-5 fractions (32.9% and 24.3%), 6-10 fractions (27.2% and 15.9%), and >10 fractions (24.1% and 14.4%). Of the patients with PRLSRT >50%, 99.6% received multifraction RT. The proportion of incomplete RT courses increased as fraction size decreased from 17.6% with 4 Gy to 34% with 2 Gy. CONCLUSIONS: Single fraction palliative RT is vastly underutilized despite no additional palliative benefit with multifraction RT. PRLSRT significantly increased with multifraction RT. In the palliative treatment of painful BMs from HCC, single fraction treatment reduces time spent receiving radiation treatments and maximizes the number of patients who complete the prescribed treatment.

The impact of socioeconomic and geographic factors on access to transoral robotic/endoscopic surgery for early stage oropharyngeal malignancy.

OBJECTIVE: To evaluate the role of social and geographic factors on the likelihood of receiving transoral robotic surgery (TORS) or non-robotic transoral endoscopic surgery treatment in early stage oropharyngeal squamous cell carcinoma (OPSCC). MATERIALS AND METHODS: The National Cancer Database was queried to form a cohort of patients with T1-T2 N0-N1 M0 OPSCC (AJCC v.7) who underwent treatment from 2010 to 2016. Demographics, tumor characteristics, treatment type, social, and geographic factors were all collected. Univariate analysis and multivariate logistic regression were then performed. RESULTS: Among 9267 identified patients, 1774 (19.1%) received transoral robotic surgery (TORS), 1191 (12.9%) received transoral endoscopic surgery, and 6302 (68%) received radiation therapy. We found that lower cancer stage, lower comorbidity burden and HPV- positive status predicted a statistically significant increased likelihood of receiving surgery. Patients who reside in suburban or small urban areas (>1 million population), were low-to- middle income, or rely on Medicaid were less likely to receive surgery. Patients that reside in Medicaid-expansion states were more likely to receive TORS (p > .0001). Patients that reside in states that expanded Medicaid January 2014 and after were more likely to receive non-robotic transoral endoscopic surgery (p > .0001). CONCLUSIONS: Poorer baseline health, lower socioeconomic status and residence in small urban areas may act as barriers to accessing minimally invasive transoral surgery while residence in a Medicaid-expansion state may improve access. Barriers to accessing robotic surgery may be greater than accessing non-robotic surgery.

Dosimetry Comparison of Palliative Radiation Plans Generated From Available Diagnostic CT Images Versus Dedicated CT Simulation for Inpatients.

Introduction The morbidity sequelae of advanced cancer are often irreversible. Early palliative radiation can prevent, delay, and even improve these consequences. Treatment may be delayed due to a packed computed tomography (CT) simulation schedule or other logistics, including the cost and burden of arranging ambulance transportation when radiation centers are off-site. Objectives The primary objective was to determine the feasibility of using a recent diagnostic CT scan in lieu of a dedicated simulation CT to generate an adequate plan without sacrificing dosimetric goals and subsequent efficacy or tolerability. Secondary objectives included how much the lesion has grown, and how much earlier treatment could start if planned on a diagnostic CT scan. Materials/Methods For each inpatient treated with palliative radiation, a prior recent diagnostic CT scan was imported into the RayStation (RaySearch Laboratories, Stockholm, Sweden) planning system. From these diagnostic scans, planning treatment volumes (PTV) and organs at risk (OAR) were contoured using the same technique as the patient's actual treatment. The primary outcome was to compare both the PTV coverage and OAR dose between the plan generated from the diagnostic CT compared to that from the simulation CT. Our secondary outcomes include the mean time between CT simulation and first treatment, change in tumor volume between diagnostic scan and CT simulation, and the hottest 1% of each plan (D1). Results Between May and August 2019, a total of 22 inpatients were treated palliatively. Of those 22 patients, 10 patients (ages 32-92 years, median 64.5 years, 50% spine) met study criteria and had a diagnostic CT scan that was obtained within 14 days of simulation CT that was also compatible with our planning software. In the plans that were delivered, a mean of 98.8% (range 94.4-100%) of PTV was covered by at least 95% prescription dose. In the diagnostic CT plans, a mean of 95.4% (range 84.5-100%) of PTV was covered by at least 95% prescription dose. The difference between plans trended towards significance (p=0.061). When looking at patients receiving treatment to the spine or having a diagnostic CT within four days of the simulation CT, there was no statistically significant difference between the two plans (p=0.032 and 0.030, respectively). The OARs received, on average, 1.4% less mean radiation dose in the hypothetical plans (p=0.911). All OAR constraints were met in both groups. The mean time between diagnostic CT and CT simulation was 5.9 days and between CT simulation and first treatment was 1.9 days (range 0-5 days). The mean change in tumor volume was 22.64% smaller in the diagnostic CT scan plan. The D1 was an average 1% hotter in the hypothetical plans (p=0.16). Conclusion In hospitalized patients with an indication for palliative radiation, treatment planning on a pre-existing recent diagnostic CT scan produces comparable dose distributions without increases in dose to OARs when compared to the use of CT simulation scans, particularly for the treatment of the spine or when a very recent diagnostic CT is available. Bypassing CT simulation in select cases allows for earlier delivery of radiation with less patient and logistical burden. In combination with daily image guidance, this may translate to more timely delivery of radiation, less cost and burden to critically ill patients, and improved palliative benefit.

Systematic review of postoperative therapy for resected squamous cell carcinoma of the head and neck: Executive summary of the American Radium Society appropriate use criteria.

BACKGROUND: The aims of this systematic review are to (a) evaluate the current literature on the impact of postoperative therapy for resected squamous cell carcinoma of the head and neck (SCCHN) on oncologic and non-oncologic outcomes and (b) identify the optimal evidence-based postoperative therapy recommendations for commonly encountered clinical scenarios. METHODS: An analysis of the medical literature from peer-reviewed journals was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline. Prospective studies and methodology-based systematic reviews and meta-analyses of postoperative therapy for SCCHN were identified by searching Medline (OVID) and EMBASE (Elsevier) using controlled vocabulary terms (ie, National Library of Medicine Medical Subject Headings [MeSH], EMTREE). Study screening and selection was performed with Covidence software and full-text review. The RAND/UCLA appropriateness method was used by the expert panel to rate the appropriate use of postoperative therapy, and the modified Delphi method was used to come to consensus. RESULTS: A total of 5660 studies were identified and screened using the title and abstract, leading to 201 studies assessed for relevance using full-text review. After limitation to the eligibility criteria, 101 studies from 1977 to 2020 were identified, including 77 with oncologic endpoints and 24 with function and quality of life endpoints. All studies reported staging prior to the implementation of American Joint Committee on Cancer (AJCC-8). CONCLUSIONS: Prospective clinical studies and systematic reviews identified through the PRISMA systematic review provided good evidence for consensus statements regarding the appropriate use of postoperative therapy for resected SCCHN. Further research is needed in domains where consensus by the expert panel could not be achieved for the appropriateness of specific postoperative therapeutic interventions.

The influence of breast cancer subtype on survival after palliative radiation for osseous metastases.

BACKGROUND: Among patients with osseous metastases, breast cancer (BC) patients typically have the best prognosis. In the palliative setting, BC is often considered a single disease, but based on receptor status there are four distinct subtypes: luminal A (LA), luminal B (LB), triple negative (TN), and HER2-enriched (HER2). We hypothesize that survival and palliative outcomes following palliative RT for osseous metastases correlate with breast cancer subtype (BCS). METHODS: We identified 3,895 BC patients with known receptor status who received palliative RT for osseous metastases from 2004-2013 in the National Cancer Database. Kaplan-Meier method with log-rank testing and univariate/multivariate Cox-regression was used to identify survival factors. Incomplete radiation courses, 30-day mortality rate, and percentage remaining life spent receiving RT (PRLSRT) were calculated. RESULTS: Subtypes were 54% LA, 33% LB, 8% TN, and 5% HER2 with median survival of 34.1, 28.2, 5.3, and 15.7 months, respectively (p < 0.001). Overall 82% of patients received ≥10 fractions. Although BCS had limited effect on radiation regimens, TN received nearly twice as many single or hypofractionated (≤5 fractions) treatments, but the overall rate of these fraction schemes was low at 3.7 and 13.7%, respectively. Compared to LA and LB, TN and HER2 patients had worse palliative outcomes; higher rates of incomplete courses at 18.8% and 18.3% versus 12.7%-14.4%; higher 30-day mortality post-radiotherapy at 21.5% and 16.0% versus 6.3%-7.9%, and higher median PRLSRT of 7.7% and 3.7% versus 2.2%-2.4% for LA and LB. On multivariate analysis, BCS was associated with overall survival with TN (HR 3.7), HER2 (HR 1.75), and LB (HR 1.28) fairing worse than LA (p < 0.001). CONCLUSIONS: BCS correlated with survival and palliative outcome following radiation to osseous metastases. BCS should be considered by physicians when planning palliative RT to maximize quality-of-life, avoid unnecessary treatment, and ensure palliative benefits.

Neoadjuvant chemotherapy improves survival compared with concurrent chemoradiation alone in nasopharyngeal carcinoma patients with N3 disease.

BACKGROUND: Neoadjuvant chemotherapy (NAC) trials in endemic regions of nasopharyngeal carcinoma (NPC) found improved survival, but studies are lacking in nonendemic regions. We assessed whether adding NAC to concurrent chemoradiation (CRT) improves overall survival (OS), especially in high-risk nonendemic patients. METHODS: Definitively treated NPC patients (n = 5424) from the National Cancer Database were analyzed for predictors of NAC and NAC effects on OS with multivariate Cox proportional hazards analysis (multivariate analysis [MVA]). Propensity score matched (1:2) survival analysis of NAC (n = 968) and CRT alone (n = 1914) was also performed. Effects on OS were stratified by risk group. RESULTS: On MVA, NAC-improved OS among the total cohort (hazard ratio [HR] 0.89, P = .049), particularly among stratified keratinizing histology (HR 0.82, P = .015) and N3 disease (HR 0.73, P = .046). Among propensity matched patients, NAC improved OS in patients with N3 disease (n = 336; HR 0.71, P = .046). CONCLUSIONS: NAC may improve OS among nonendemic NPC patients at higher risk of distant micrometastases, particularly N3 disease and those with unfavorable histology.

The Dosimetric Impact of Interfractional Organ-at-Risk Movement During Liver Stereotactic Body Radiation Therapy.

PURPOSE: Stereotactic body radiation therapy (SBRT) is an effective therapy for treating liver malignancies. However, little is known about interfractional dose variations to adjacent organs at risk (OARs). We examine the effects of interfractional organ movement and setup variation on dose delivered to OARs in patients receiving liver SBRT. METHODS AND MATERIALS: Thirty patients treated with liver SBRT were analyzed. Daily image guidance with diagnostic quality computed tomography-on-rails imaging was performed before each fraction. In phase 1, these daily images were used to delineate all OARs including the liver, heart, right kidney, esophagus, stomach, duodenum, and large bowel in 10 patients. In phase 2, only OARS in close proximity to the target were contoured in 20 additional patients. Dose distribution on each daily computed tomography was generated, and daily doses to each OAR were recorded and compared with clinical thresholds to determine whether a daily dose excess (DDE) occurred. RESULTS: In phase 1, significant interfractional dose differences between planned and delivered dose to OARs were observed, but differences were rarely clinically significant, with just 1 DDE. In phase 2, multiple DDEs were recorded for OARs close to the target, mainly involving the stomach, heart, and esophagus. Tumors in the hilum and liver segments I, IV, and VIII were the most common locations for DDEs. On root cause analysis, 3 etiologies of DDE emerged: craniocaudal shift (69.2%), anatomic changes (28.2%), and anteroposterior shifts (2.6%). CONCLUSIONS: OARs close to liver lesions may receive higher doses than expected during SBRT owing to interfractional variations in OARs relative to the target. These differences in planned versus expected dose can lead to toxicity. Efforts to better evaluate OARs with daily image guidance may help reduce risks. Application of adaptive replanning and improved and real-time image guidance could mitigate risks of toxicity, and further study into their applications is warranted.

Stereotactic body radiation therapy for hepatocellular carcinoma: Practice patterns, dose selection and factors impacting survival.

BACKGROUND: Stereotactic body radiation therapy (SBRT) is an emerging option for unresectable hepatocellular carcinoma (HCC) without consensus regarding optimal dose schemas. This analysis identifies practice patterns and factors that influence dose selection and overall survival, with particular emphasis on dose and tumor size. MATERIALS/METHODS: Query of the National Cancer Database (NCDB) identified patients with unresectable, nonmetastatic HCC who received SBRT from 2004 to 2013. Biological Effective Dose (BED) was calculated for each patient in order to uniformly analyze different fractionation regimens. RESULTS: A total of 456 patients met the inclusion criteria. The median BED was 100 Gy (22.5-208.0), which corresponded to the most common dose fractionation (50 Gy in five fractions). Various factors influenced dose selection including tumor size (P < 0.001), tumor stage (P = 0.002), and facility case volume (<0.001). On multivariate analysis, low BED (<75 Gy, HR 2.537, P < 0.001; 75-100 Gy, HR 1.986, P = 0.007), increasing tumor size (HR 1.067, P = 0.032), elevated AFP (HR 1.585, P = 0.019), stage 3 (HR 1.962, P < 0.001), low-volume facilities (1-5 cases HR 1.687, P = 0.006), and a longer time interval from diagnosis to SBRT (>2 to ≤4 months, HR 1.456, P = 0.048; >4 months, HR 2.192, P < 0.001) were associated with worse survival. CONCLUSION: SBRT use is increasing for HCC, and multiple regimens are clinically employed. Although high BED was associated with improved outcomes, multiple factors contributed to the dose selection with favorable patients receiving higher doses. Continued efforts to enhance radiation planning and delivery may help improve utilization, safety, and efficacy.

Technical Note: Enhancing soft tissue contrast and radiation-induced image changes with dual-energy CT for radiation therapy.

PURPOSE: The purpose of this work is to investigate the use of low-energy monoenergetic decompositions obtained from dual-energy CT (DECT) to enhance image contrast and the detection of radiation-induced changes of CT textures in pancreatic cancer. METHODS: The DECT data acquired for 10 consecutive pancreatic cancer patients during routine nongated CT-guided radiation therapy (RT) using an in-room CT (Definition AS Open, Siemens Healthcare, Malvern, PA) were analyzed. With a sequential DE protocol, the scanner rapidly performs two helical acquisitions, the first at a tube voltage of 80 kVp and the second at a tube voltage of 140 kVp. Virtual monoenergetic images across a range of energies from 40 to 140 keV were reconstructed using an image-based material decomposition. Intravenous (IV) bolus-free contrast enhancement in pancreas patient tumors was measured across a spectrum of monoenergies. For treatment response assessment, the changes in CT histogram features (including mean CT number (MCTN), entropy, kurtosis) in pancreas tumors were measured during treatment. The results from the monoenergetic decompositions were compared to those obtained from the standard 120 kVp CT protocol for the same subjects. RESULTS: Data of monoenergetic decompositions of the 10 patients confirmed the expected enhancement of soft tissue contrast as the energy is decreased. The changes in the selected CT histogram features in the pancreas during RT delivery were amplified with the low-energy monoenergetic decompositions, as compared to the changes measured from the 120 kVp CTs. For the patients studied, the average reduction in the MCTN in pancreas from the first to the last (the 28th) treatment fraction was 4.09 HU for the standard 120 kVp and 11.15 HU for the 40 keV monoenergetic decomposition. CONCLUSIONS: Low-energy monoenergetic decompositions from DECT substantially increase soft tissue contrast and increase the magnitude of radiation-induced changes in CT histogram textures during RT delivery for pancreatic cancer. Therefore, quantitative DECT may assist the detection of early RT response.

Palliative interventions for hepatocellular carcinoma patients: analysis of the National Cancer Database.

BACKGROUND: Palliative therapies are provided to a subset of hepatocellular carcinoma (HCC) patients with the aim of providing symptomatic relief, better quality of life and improved survival. The present study sought to assess and compare the efficacy of different palliative therapies for HCC. METHODS: The National Cancer Database (NCDB), a retrospective national database that captures approximately 70% of all patients treated for cancer in the US, was queried for patients with HCC who were deemed unresectable from 1998-2011. Patients were stratified by receipt of palliative therapy. Survival analysis was examined by log-rank test and Kaplan Meier curves, and a multivariate proportional hazards model was utilized to identify the predictors of survival. RESULTS: A total of 3,267 patients were identified; 287 (8.7%) received surgical palliation, 827 (25.3%) received radiotherapy (RT), 877 (26.8%) received chemotherapy, 1,067 (32.6%) received pain management therapy, while 209 (6.4%) received a combination of the previous three modalities. On multivariate analysis palliative RT was identified as a positive predictor of survival [hazards ratio (HR) 0.65; 95% CI, 0.50-0.83]. Stratifying by disease stage, palliative RT provided a significant survival benefit for patients with stage IV disease. CONCLUSIONS: Palliative RT appears to extend survival and should be considered for patients presenting with late stage HCC.

Stereotactic Body Radiotherapy for Elderly Patients With Medically Inoperable Pancreatic Cancer.

OBJECTIVES: People over the age of 75 years account for approximately 40% of patients diagnosed with pancreatic cancer, many with comorbidities that may limit their treatment options. This study reports on the use of stereotactic body radiation therapy (SBRT) in this population. MATERIALS AND METHODS: Twenty consecutively treated patients over the age of 75 with pathologically proven localized pancreatic cancer were included in this retrospective review. All had been evaluated by a multidisciplinary team as unable to tolerate surgery or combined chemoradiation therapy. Patient outcomes were analyzed to determine the safety and efficacy of SBRT in this elderly cohort. RESULTS: The median age was 83.2 years (minimum 77 y, maximum 90 y). Eighteen patients were treated at time of initial diagnosis, and 2 for recurrence after surgery. Eleven (55%) of the patients had an Adult Comorbidity Evaluation-27 comorbidity index score of 3 (severe) and 6 (30%) had a score of 2 (moderate). Fourteen patients were treated with 35 Gy in 5 fractions, 5 with 30 Gy in 5 fractions, and 1 patient with 36 Gy in 3 fractions. Seven (35%) patients had common terminology criteria for adverse events (CTCAE) V4.0 toxicity grade of 1-2, and 3 patients had a CTCAE V4.0 toxicity grade of 3-4, 2 with dehydration, and 1 had episodes of gastrointestinal bleeding. Three patients recurred locally, 10 had distant metastases, 4 of whom were found on the first posttreatment scan. Median overall survival was 6.4 months (95% confidence interval, 3.5-10.8 mo). Median recurrence-free survival was 6.8 months (95% confidence interval, 1.3-23.5 mo). Two patients survived >23 months. CONCLUSION: SBRT for pancreatic cancer appears to be a safe and effective method for treatment of elderly patients, even in the setting of severe comorbidities.

Predictive Capacity of 3 Comorbidity Indices in Estimating Survival Endpoints in Women With Early-Stage Endometrial Carcinoma.

OBJECTIVE: The negative impact of comorbidity on survival in women with endometrial carcinoma (EC) is well-known. Few validated comorbidity indices are available for clinical use, such as the Charlson Comorbidity Index (CCI), the Age-Adjusted CCI (AACCI), and the Adult Comorbidity Evaluation-27 (ACE-27). The aim of the study is to determine which index best correlates with survival endpoints in women with EC. MATERIALS AND METHODS: We identified 1132 women with early-stage EC treated at an academic center. Three scores were calculated for each patient using CCI, AACCI, and ACE-27 at the time of hysterectomy. Univariate and multivariable modeling was used to determine predictors of survival. RESULTS: For each of the studied comorbidity indices, the highest scores were significantly correlated with poorer overall survival. The hazard ratio of death from any cause was 3.92 for AACCI, 2.25 for CCI, and 1.57 for ACE-27. All 3 indices were independent predictors of overall survival with a P value of less than 0.001 on multivariate analysis. In addition, lymphovascular space invasion, lower uterine segment involvement, and tumor grade were predictors of overall survival. Lymphovascular space invasion, grade (P < 0.001), and high AACCI score were the only significant predictors of recurrence-free survival (RFS). Lymphovascular space invasion and tumor grade were the only 2 predictors of disease-specific survival. CONCLUSIONS: Although all 3 studied comorbidity indices were significant predictors of overall survival in women with early-stage EC, AACCI showed a stronger association. It should be considered for evaluating comorbidity in women with early-stage EC.

Radiosurgery of multiple brain metastases with single-isocenter dynamic conformal arcs (SIDCA).

PURPOSE: To propose single-isocenter dynamic conformal arcs (SIDCA), a novel technique for radiosurgery of multiple brain metastases, and to compare SIDCA with volumetric modulated arc therapy (VMAT) and multiple-isocenter dynamic conformal arcs (MIDCA) for plan quality. METHODS AND MATERIALS: SIDCA, MIDCA, and VMAT plans were created on 6 patients with 3-5 metastases. Plans were evaluated using Radiation Therapy Oncology Group conformity index (RCI), Paddick conformity index (PCI), gradient index (GI), volumes that received more than 100% (V(100%)), 50% (V(50%)), 25% (V(25%)) and 10% (V(10%)) of prescription dose, total monitor units (MUs), and delivery time (DT). RESULTS: SIDCA achieved conformal plans (RCI = 1.38 ± 0.12, PCI = 0.72 ± 0.06) with steep dose fall-off (GI = 3.97 ± 0.51). MIDCA plans had comparable plan quality and MUs as SIDCA, but 52% longer DT. The VMAT plans had better conformity (RCI = 1.15 ± 0.09, p < 0.01 and PCI = 0.86 ± 0.06, p < 0.01) than SIDCA, worse GI (4.34 ± 0.46, p < 0.01), higher V(25%) (p = 0.05) and V(10%) (p = 0.02), 49% less MUs and 46% shorter DT. CONCLUSIONS: All three techniques achieved conformal plans with steep dose fall-off from targets. SIDCA plans had similar plan quality as MIDCA but more efficient to delivery. SIDCA plans had lower peripheral dose spread than VMAT; VMAT plans had better conformity and faster delivery time than SIDCA.

ACR Appropriateness Criteria® pre-irradiation evaluation and management of brain metastases.

Pretreatment evaluation is performed to determine the number, location, and size of the brain metastases and magnetic resonance imaging (MRI) is the recommended imaging technique, particularly in patients being considered for surgery or stereotactic radiosurgery. A contiguous thin-cut volumetric MRI with gadolinium with newer gadolinium-based agents can improve detection of small brain metastases. A systemic workup and medical evaluation are important, given that subsequent treatment for the brain metastases will also depend on the extent of the extracranial disease and on the age and performance status of the patient. Patients with hydrocephalus or impending brain herniation should be started on high doses of corticosteroids and evaluated for possible neurosurgical intervention. Patients with moderate symptoms should receive approximately 4-8 mg/d of dexamethasone in divided doses. The routine use of corticosteroids in patients without neurologic symptoms is not necessary. There is no proven benefit of anticonvulsants in patient without seizures. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

A novel approach for establishing benchmark CBCT/CT deformable image registrations in prostate cancer radiotherapy.

Deformable image registration (DIR) is an integral component for adaptive radiation therapy. However, accurate registration between daily cone-beam computed tomography (CBCT) and treatment planning CT is challenging, due to significant daily variations in rectal and bladder fillings as well as the increased noise levels in CBCT images. Another significant challenge is the lack of 'ground-truth' registrations in the clinical setting, which is necessary for quantitative evaluation of various registration algorithms. The aim of this study is to establish benchmark registrations of clinical patient data. Three pairs of CT/CBCT datasets were chosen for this institutional review board approved retrospective study. On each image, in order to reduce the contouring uncertainty, ten independent sets of organs were manually delineated by five physicians. The mean contour set for each image was derived from the ten contours. A set of distinctive points (round natural calcifications and three implanted prostate fiducial markers) were also manually identified. The mean contours and point features were then incorporated as constraints into a B-spline based DIR algorithm. Further, a rigidity penalty was imposed on the femurs and pelvic bones to preserve their rigidity. A piecewise-rigid registration approach was adapted to account for the differences in femur pose and the sliding motion between bones. For each registration, the magnitude of the spatial Jacobian (|JAC|) was calculated to quantify the tissue compression and expansion. Deformation grids and finite-element-model-based unbalanced energy maps were also reviewed visually to evaluate the physical soundness of the resultant deformations. Organ DICE indices (indicating the degree of overlap between registered organs) and residual misalignments of the fiducial landmarks were quantified. Manual organ delineation on CBCT images varied significantly among physicians with overall mean DICE index of only 0.7 among redundant contours. Seminal vesicle contours were found to have the lowest correlation amongst physicians (DICE = 0.5). After DIR, the organ surfaces between CBCT and planning CT were in good alignment with mean DICE indices of 0.9 for prostate, rectum, and bladder, and 0.8 for seminal vesicles. The Jacobian magnitudes |JAC| in the prostate, rectum, and seminal vesicles were in the range of 0.4-1.5, indicating mild compression/expansion. The bladder volume differences were larger between CBCT and CT images with mean |JAC| values of 2.2, 0.7, and 1.0 for three respective patients. Bone deformation was negligible (|JAC| = ∼ 1.0). The difference between corresponding landmark points between CBCT and CT was less than 1.0 mm after DIR. We have presented a novel method of establishing benchmark DIR accuracy between CT and CBCT images in the pelvic region. The method incorporates manually delineated organ surfaces and landmark points as well as pixel similarity in the optimization, while ensuring bone rigidity and avoiding excessive deformation in soft tissue organs. Redundant contouring is necessary to reduce the overall registration uncertainty.