Long-Term Update of NRG/RTOG 0522: A Randomized Phase 3 Trial of Concurrent Radiation and Cisplatin With or Without Cetuximab in Locoregionally Advanced Head and Neck Cancer.

PURPOSE: The combination of cisplatin and radiation or cetuximab and radiation improves overall survival of patients with locoregionally advanced head and neck carcinoma. NRG Oncology conducted a phase 3 trial to test the hypothesis that adding cetuximab to radiation and cisplatin would improve progression-free survival (PFS). METHODS AND MATERIALS: Eligible patients with American Joint Committee on Cancer sixth edition stage T2 N2a-3 M0 or T3-4 N0-3 M0 were accrued from November 2005 to March 2009 and randomized to receive radiation and cisplatin without (arm A) or with (arm B) cetuximab. Outcomes were correlated with patient and tumor features. Late reactions were scored using Common Terminology Criteria for Adverse Events (version 3). RESULTS: Of 891 analyzed patients, 452 with a median follow-up of 10.1 years were alive at analysis. The addition of cetuximab did not improve PFS (hazard ratio [HR], 1.06; 95% confidence interval [CI], 0.89-1.26; P = .74), with 10-year estimates of 43.6% (95% CI, 38.8- 48.4) for arm A and 40.2% (95% CI, 35.4-45.0) for arm B. Cetuximab did not reduce locoregional failure (HR, 1.21; 95% CI, 0.95-1.53; P = .94) or distant metastasis (HR, 0.79; 95% CI, 0.54-1.14; P = .10) or improve overall survival (HR, 0.97; 95% CI, 0.80-1.16; P = .36). Cetuximab did not appear to improve PFS in either p16-positive oropharynx (HR, 1.30; 95% CI, 0.87-1.93) or p16-negative oropharynx or nonoropharyngeal primary (HR, 0.94; 95% CI, 0.73-1.21). Grade 3 to 4 late toxicity rates were 57.4% in arm A and 61.3% in arm B (P = .26). CONCLUSIONS: With a median follow-up of more than 10 years, this updated report confirms the addition of cetuximab to radiation therapy and cisplatin did not improve any measured outcome in the entire cohort or when stratifying by p16 status.

NRG Oncology/RTOG1205: A Randomized Phase II Trial of Concurrent Bevacizumab and Reirradiation Versus Bevacizumab Alone as Treatment for Recurrent Glioblastoma.

PURPOSE: To assess whether reirradiation (re-RT) and concurrent bevacizumab (BEV) improve overall survival (OS) and/or progression-free survival (PFS), compared with BEV alone in recurrent glioblastoma (GBM). The primary objective was OS, and secondary objectives included PFS, response rate, and treatment adverse events (AEs) including delayed CNS toxicities. METHODS: NRG Oncology/RTOG1205 is a prospective, phase II, randomized trial of re-RT and BEV versus BEV alone. Stratification factors included age, resection, and Karnofsky performance status (KPS). Patients with recurrent GBM with imaging evidence of tumor progression ≥ 6 months from completion of prior chemo-RT were eligible. Patients were randomly assigned 1:1 to re-RT, 35 Gy in 10 fractions, with concurrent BEV IV 10 mg/kg once in every 2 weeks or BEV alone until progression. RESULTS: From December 2012 to April 2016, 182 patients were randomly assigned, of whom 170 were eligible. Patient characteristics were well balanced between arms. The median follow-up for censored patients was 12.8 months. There was no improvement in OS for BEV + RT, hazard ratio, 0.98; 80% CI, 0.79 to 1.23; P = .46; the median survival time was 10.1 versus 9.7 months for BEV + RT versus BEV alone. The median PFS for BEV + RT was 7.1 versus 3.8 months for BEV, hazard ratio, 0.73; 95% CI, 0.53 to 1.0; P = .05. The 6-month PFS rate improved from 29.1% (95% CI, 19.1 to 39.1) for BEV to 54.3% (95% CI, 43.5 to 65.1) for BEV + RT, P = .001. Treatment was well tolerated. There were a 5% rate of acute grade 3+ treatment-related AEs and no delayed high-grade AEs. Most patients died of recurrent GBM. CONCLUSION: To our knowledge, NRG Oncology/RTOG1205 is the first prospective, randomized multi-institutional study to evaluate the safety and efficacy of re-RT in recurrent GBM using modern RT techniques. Overall, re-RT was shown to be safe and well tolerated. BEV + RT demonstrated a clinically meaningful improvement in PFS, specifically the 6-month PFS rate but no difference in OS.

Resection and radiotherapy for intracranial ependymoma: a multiinstitutional 50-year experience.

OBJECTIVE: Maximal safe resection is the standard-of-care treatment for adults with intracranial ependymoma. The value of adjuvant radiotherapy remains unclear as these tumors are rare and current data are limited to a few retrospective cohort studies. In this study, the authors assembled a cohort of patients across multiple international institutions to assess the utility of adjuvant radiotherapy in this patient population. METHODS: Adults with intracranial ependymoma managed surgically at the University Health Network in Toronto, Canada, the University of Oklahoma Health Sciences Center in Oklahoma City, Oklahoma, and The Ottawa Hospital in Ottawa, Canada, were included in this study. The primary end points were progression-free survival (PFS) and overall survival (OS). Clinicopathological variables were assessed in univariate and multivariate Cox proportional hazard models for prognostic significance of PFS and OS. RESULTS: A total of 122 patients diagnosed between 1968 and 2019 were identified for inclusion. The majority of patients had grade II ependymomas on histopathology (78%) that were infratentorially located (71%), underwent gross-total (GTR) or near-total resection (NTR; 55%), and were treated with adjuvant radiotherapy (67%). A volumetric analysis of the extent of resection in 49 patients with available tumor volume data supported the accuracy of the categorical GTR, NTR, and subtotal resection (STR) groups utilized. Independent statistically significant predictors of poorer PFS in the multivariate analysis included STR or biopsy (vs GTR/NTR; HR 5.4, 95% confidence interval [CI] 2.4-11.0, p < 0.0001) and not receiving adjuvant radiotherapy; cranial (HR 0.5, 95% CI 0.2-1.1) and craniospinal (HR 0.2, 95% CI 0.04-0.5) adjuvant radiotherapy regimens improved PFS (p = 0.0147). Predictors of poorer OS in the multivariate analysis were grade III histopathology (vs grade II: HR 5.7, 95% CI 1.6-20.2, p = 0.0064) and undergoing a biopsy/STR (vs GTR/NTR: HR 9.8, 95% CI 3.2-30.1, p = 0.0001). CONCLUSIONS: The results of this 50-year experience in treating adult intracranial ependymomas confirm an important role for maximal safe resection (ideally GTR or NTR) and demonstrate that adjuvant radiotherapy improves PFS. This work will guide future studies as testing for molecular ependymoma alterations become incorporated into routine clinical practice.

Treatment of Recurrent Optic Nerve Sheath Meningioma With a Secondary Course of Radiotherapy.

Optic nerve sheath meningiomas (ONSM) are benign neoplasms found surrounding the optic nerve that can affect vision, and potentially lead to blindness. The use of radiotherapy has been advocated to improve visual outcomes and minimize the risk of complications. We present a case of a 58-year-old woman who was treated with a second course of radiotherapy 27-years after initial radiotherapy for recurrent ONSM. The patient responded well to the second course of radiotherapy with good clinical and visual outcomes. This case report supports evidence that treatment with radiotherapy can improve visual outcomes in patients with recurrent ONSM with mild to moderate re-irradiation-related side effects.

A prospective single-institution study of intraoperative radiotherapy (IORT) for early-stage breast cancer.

Intraoperative radiation therapy (IORT) is an option for breast-conserving therapy in early-stage breast cancer. IORT is given in one fraction at the time of surgery and eliminates the need for adjuvant external beam radiation therapy. However, previous trials indicate increased local failure rates compared with whole-breast irradiation, which engenders controversy around the appropriate use of IORT. We conducted a prospective study of patients diagnosed with early-stage breast cancer (T1-T2, N0-N1) at the University of Oklahoma Health Sciences Center (OUHSC) between 2013 and 2017 and treated with lumpectomy followed by intraoperative radiation therapy (IORT). Data collected included stage of disease, tumor location, histology, tumor markers, lymph node status, surgical margin size, recurrence, cosmetic outcomes, and length of follow-up. In-breast tumor recurrence rate (IBTR) in the 77 evaluable patients was 3.9% (3 patients). Margins were close (1 mm or less) in all three recurrent patients, and two were initially diagnosed with DCIS. Recurrence rates in our patients were comparable to prior reports. All recurrences were in patients with close margins indicating that this may represent a predictive feature for exclusion from IORT; additional studies are essential to determine the recurrence rates among patients treated with IORT and to identify potential predictors of IORT eligibility.

Laser Interstitial Thermal Therapy for Metastatic Melanoma After Failed Radiation Therapy: A Case Series.

BACKGROUND: Laser interstitial thermal therapy (LITT) is a growing technology to treat a variety of brain lesions. It offers an alternative to treatment options, such as open craniotomy and stereotactic radiosurgery. OBJECTIVE: To analyze our experience using LITT for metastatic melanoma. METHODS: This is a retrospective chart review of the patients from our institution. Our case series involves 5 patients who had previously failed radiation treatment. RESULTS: Our patients have low complication rates and short hospital stays. Both are considerably lower when compared to the literature for metastatic melanoma. CONCLUSION: LITT is a safe therapy, with few complications and short hospital stays.

Bilateral Carotid-cavernous Fistulas Treated with Partial Embolization and Radiosurgery.

Bilateral carotid-cavernous fistulas (CCFs) are rare. In this paper, we report the case of an 88-year-old woman who presented with a two-month history of worsening visual symptoms and was subsequently found to have bilateral Barrow grade D CCFs. Cannulation and complete embolization of the offending vessels during angiography proved unsuccessful, and so the patient underwent adjuvant radiosurgery as salvage therapy with a good clinical outcome. This case adds to the limited but growing literature on the multi-modal management of CCFs.

Factors Associated with Treatment Failure and Radiosurgery-Related Edema in WHO Grade 1 and 2 Meningioma Patients Receiving Gamma Knife Radiosurgery.

BACKGROUND: Before the advent of radiosurgery, neurosurgical treatment of meningiomas typically involved gross total resection of the mass whenever surgery was deemed possible. Over the past 4 decades, though, Gamma Knife radiosurgery (GKRS) has proved to be an effective, minimally invasive means to control the growth of these tumors. However, the variables associated with treatment failure (regrowth or clinical progression) after GKRS and GKRS-related complications, such as cerebral edema, are less well understood. METHODS: We retrospectively collected data between 2009 and 2018 for patients who underwent GKRS for meningiomas. After data collection, we performed univariate and multivariable modeling of the factors that predict treatment failure and cerebral edema after GKRS. Hazard ratios (HR) and P values were determined for these variables. RESULTS: Fifty-two patients were included our analysis. The majority of patients were female (38/52,73%), and nearly all patients presented with a suspected or confirmed World Health Organization grade 1 meningioma (48/52, 92%). The median tumor volume was 3.49 cc (range, 0.22-20.11 cc). Evidence of meningioma progression after treatment developed in 5 patients (10%), with a median time to continued tumor growth of 5.9 months (range, 2.7-18.3 months). In multivariable analysis, patients in whom treatment failed were more likely to be male (HR = 8.42, P = 0.045) and to present with larger tumor volumes (HR = 1.27, P = 0.011). In addition, 5 patients (10%) experienced treatment-related cerebral edema. On univariate analysis, patients who experienced cerebral edema were more likely present with larger tumors (HR = 1.16, P = 0.028). CONCLUSIONS: Increasing meningioma size and male gender predispose to meningioma progression after treatment with GKRS. Increasing tumor size also predicts the development of postradiosurgery cerebral edema.

Clinicopathologic Features and Radiation Therapy Utilization in Patients with Male Breast Cancer: A National Cancer Database Study.

Male breast cancer (MBC) accounts for approximately 1% of all breast cancers, limiting the data characterizing clinicopathologic features and treatment outcomes in patients with MBC. This paucity of data has led to most of our treatment guidance being extrapolated from patients with female breast cancer (FBC). From 1998 to 2012, data were captured using the National Cancer Database to identify patients with nonmetastatic MBC (n = 23 305) and FBC (n = 2 678 061). Tumor and clinicopathologic features were obtained and compared. Patients with MBC were more likely to have invasive disease, T2-4 tumors, centrally located tumors, positive lymph nodes, estrogen receptor-positive or progesterone receptor-positive tumors, lymphovascular space invasion, and were less likely to have Her2/neu-positive or triple-negative tumors. All of these differences were statistically significant (P < .001). Treatment comparisons showed that patients with MBC were more likely to undergo mastectomy and less likely to undergo breast-conserving surgery with postoperative radiation utilization found to be less in patients with MBC, both as part of breast-conserving therapy (BCT) and for postmastectomy radiation treatment (PMRT) (P < .001). Stage-by-stage comparisons showed that median survival, 5-year, and 10-year overall survival (OS) rates are lower in patients with MBC vs patients with FBC (P < .001). The utilization of adjuvant radiation, both BCT and PMRT, was shown to improve 5- and 10-year OS (P < .001). Male breast cancer clinicopathologic features appear to be unfavorable in relation to FBC and adjuvant radiation is shown beneficial in survival outcomes. Further investigation is needed to help guide future utilization and treatment with radiation, systemic, and endocrine manipulation in this small population of patients with MBC.

Comparison of Volumetric Modulated Arc Therapy and Intensity Modulated Radiation Therapy for Whole Brain Hippocampal Sparing Treatment Plans Based on Radiobiological Modeling.

INTRODUCTION: In this article, we report the results of our investigation on comparison of radiobiological aspects of treatment plans with linear accelerator-based intensity-modulated radiation therapy and volumetric-modulated arc therapy for patients having hippocampal avoidance whole-brain radiation therapy. MATERIALS AND METHODS: In this retrospective study using the dose-volume histogram, we calculated and compared biophysical indices of equivalent uniform dose, tumor control probability, and normal tissue complication probability (NTCP) for 15 whole-brain radiotherapy patients. RESULTS AND DISCUSSIONS: Dose-response models for tumors and critical structures were separated into two groups: mechanistic and empirical. Mechanistic models formulate mathematically with describable relationships while empirical models fit data through empirical observations to appropriately determine parameters giving results agreeable to those given by mechanistic models. CONCLUSIONS: Techniques applied in this manuscript could be applied to any other organs or types of cancer to evaluate treatment plans based on radiobiological modeling.

Dosimetric comparison of sector-blocked and non-sector-blocked Gamma Knife Perfexion treatment plans for trigeminal neuralgia.

The purpose of this study is to compare the quality of trigeminal neuralgia (TN) treatment plans with and without utilizing sector blocking. Twelve patients with 13 cases of TN were evaluated in this retrospective study. Identical magnetic resonance imaging (MRI) contour sets and prescription doses used in treatments were reused for all plans. Treatment plans were compared on the basis of the amount of dose received by critical structures (i.e., brainstem, ipsilateral temporal lobe, optic chiasm, optic nerves, cochlea) and the estimated total treatment time. The use of sector blocking resulted in a statistically significant decrease in the radiation dose to the brainstem but increased doses to the cerebellum and temporal lobe regions. The magnitude of these differences was small and individual patient anatomy specific. The use of sector blocking also resulted in a statistically significant increase in the treatment time. The magnitude of the change in treatment time was dependent on the number of sectors blocked. Our study suggests some potential benefits, as well as disadvantages, to the use of sector blocking in the treatment of TN. Treatment decision needs to be individualized based on the patient's anatomy and overall condition.

Simultaneous Resection of Multiple Metastatic Brain Tumors with Multiple Keyhole Craniotomies.

BACKGROUND: The proper management of symptomatic patients with 2 or more brain metastases is not entirely clear, and the surgical outcomes of these patients undergoing multiple simultaneous craniotomies have not been well described. In this article, we describe patient outcomes after simultaneously resecting metastatic lesions through multiple keyhole craniotomies. METHODS: We conducted a retrospective review of data obtained for all patients undergoing resection of multiple brain metastases in one operation between 2014 and 2016. We describe a technique for resecting multiple metastatic lesions and share the patient outcomes of this operation. RESULTS: Twenty patients with 46 tumor resections were included in the study. The primary site of metastases for the majority of patients was lung, followed by melanoma, renal, breast, colon, and testes. Nine of 20 (45%) patients had 2 preoperative intracranial lesions, and 11 (55%) had three or more. Karnofsky performance scales were calculated for 14 patients: postoperatively 10 of 14 (71%) scores improved, 2 of 14 (14%) worsened, and 2 of 14 (14%) remained unchanged. After surgery, 9 of 14 (64%) patients were weaned off steroids by 2-month follow-up. The overall median survival time from date of surgery was 10.8 months. CONCLUSIONS: We present patient outcomes after simultaneously resecting metastatic brain tumors through multiple keyhole craniotomies in symptomatic patients. Our results suggest comparable outcomes and similar surgical risk compared with those undergoing resection of a single brain metastasis. Resection of multiple brain metastases may improve Karnofsky Performance Scale scores in the early postoperative period and allow patients to be weaned from steroids.

When Evaluating a New Thyroid Mass and a Ring-Enhancing Brain Lesion (When Two Presentations Collide).

We aimed to evaluate the clinical and pathologic features of two common medical illnesses and their appropriate workup and pathognomonic findings. A 57-year-old white male presented with a new onset expressive aphasia while traveling abroad. He was evaluated at an outside facility and underwent workup for a stroke. The evaluation included a CT and MRI of the brain demonstrating three new enhancing lesions, the largest of which was a 2.5 cm ring-enhancing cystic lesion. A CT of the chest noted a 4-cm cystic thyroid lesion that was diagnosed as a thyroid cancer with brain metastases. The patient was told that he had cancer and needed therapy. The patient elected to be treated closer to home and presented to our institution with a referral for brain irradiation. The patient was evaluated and his case was reviewed in a neuro/oncology tumor board, where several other possible diagnoses were considered. A complete workup was performed, including two separate FNAs of the thyroid mass along with a PET scan, CEA test, CBC test, CMP, CRP, sed rate, and SLE testing, along with a spinal tap (cytology, protein, and serology). The MRI on further review showed that one of the lesions was a periventricular enhancing area and the largest lesion was an open ring with T2 and DWI enhancement. The fine needle aspiration (FNA) samples of the thyroid both showed benign histology. The laboratory evaluation was negative except for a mildly elevated CRP with no tumor markers identified and the spinal tap was positive for elevated protein and particularly oligoclonal bands. The PET scan showed no sites of fluorodeoxyglucose (FDG) avid masses including the thyroid. Multiple sclerosis (MS) represents 400,000 cases in the US and benign thyroid nodules noted on imaging range from 19-35% of the population. One pathognomonic finding of MS that is less common is the open rings called tumefactive lesions versus the closed rings seen with metastases. A cystic thyroid lesion can range from a benign process to a differentiated thyroid cancer. The rate of distant metastasis with these cancers ranges from 1-23% in the literature. Lung and bone metastasis are the most common sites with CNS metastasis only accounting for < 2% of the cases. A better understanding of these findings should allow physicians to have a higher degree of suspicion in these cases and provoke further inquiry to prevent unnecessary injury.

Radiotherapy in Patients 70 Years and Older With Triple-Negative Breast Cancer.

PURPOSE: To evaluate the use of radiotherapy (RT) in older patients with triple-negative breast cancer (TNBC). PATIENTS AND METHODS: The National Cancer Data Base (NCDB) is a comprehensive national database that captures approximately 70% of newly diagnosed cancer patients in the United States. Data for patients meeting the criteria of nonmetastatic TNBC were extracted and analyzed. RESULTS: A total of 44,731 TNBC patients with indications for postoperative RT were identified. Median patient age was 59 (range, 19-90) years. Maximum RT use occurred between the ages of 46 and 70, with rapid decline in patients older than 70 years. Overall, there was a statistically significant improvement in overall survival (OS) with the addition of RT. Of the 24 variables evaluated, 23 were statistically significant on univariate analysis. On multivariate analysis a majority of these factors including facility location, age, Charlson/Deyo comorbidity condition score, and tumor characteristics (lymph node status, pathologic T stages, and use of systemic chemotherapy) remained significant. The use of RT was associated with improved OS rates in both the older (5-year OS, 66.4% vs. 42.6%, P < .001) and younger (5-year OS, 77.3% vs. 63.2%, P < .001) patient groups. CONCLUSION: In this group of high-risk patients, there was decreased use of RT in older patients. In our study of a large patient population with TNBC, RT was associated with increased OS rates in both younger and older patients, and RT should be strongly considered, when indicated by clinicopathologic factors, in patients with TNBC.

Quantitative evaluation of patient setup uncertainty of stereotactic radiotherapy with the frameless 6D ExacTrac system using statistical modeling.

The purpose of this study is to evaluate patient setup accuracy and quantify indi-vidual and cumulative positioning uncertainties associated with different hardware and software components of the stereotactic radiotherapy (SRS/SRT) with the frameless 6D ExacTrac system. A statistical model is used to evaluate positioning uncertainties of the different components of SRS/SRT treatment with the Brainlab 6D ExacTrac system using the positioning shifts of 35 patients having cranial lesions. All these patients are immobilized with rigid head-and-neck masks, simu-lated with Brainlab localizer and planned with iPlan treatment planning system. Stereoscopic X-ray images (XC) are acquired and registered to corresponding digitally reconstructed radiographs using bony-anatomy matching to calculate 6D translational and rotational shifts. When the shifts are within tolerance (0.7 mm and 1°), treatment is initiated. Otherwise corrections are applied and additional X-rays (XV) are acquired to verify that patient position is within tolerance. The uncertain-ties from the mask, localizer, IR -frame, X-ray imaging, MV, and kV isocentricity are quantified individually. Mask uncertainty (translational: lateral, longitudinal, vertical; rotational: pitch, roll, yaw) is the largest and varies with patients in the range (-2.07-3.71 mm, -5.82-5.62 mm, -5.84-3.61 mm; -2.10-2.40°, -2.23-2.60°, and -2.7-3.00°) obtained from mean of XC shifts for each patient. Setup uncer-tainty in IR positioning (0.88, 2.12, 1.40 mm, and 0.64°, 0.83°, 0.96°) is extracted from standard deviation of XC. Systematic uncertainties of the frame (0.18, 0.25, -1.27mm, -0.32°, 0.18°, and 0.47°) and localizer (-0.03, -0.01, 0.03mm, and -0.03°, 0.00°, -0.01°) are extracted from means of all XV setups and mean of all XC distributions, respectively. Uncertainties in isocentricity of the MV radiotherapy machine are (0.27, 0.24, 0.34 mm) and kV imager (0.15, -0.4, 0.21 mm). A statisti-cal model is developed to evaluate the individual and cumulative systematic and random positioning uncertainties induced by the different hardware and software components of the 6D ExacTrac system. The uncertainties from the mask, local-izer, IR frame, X-ray imaging, couch, MV linac, and kV imager isocentricity are quantified using statistical modeling.

Dosimetric comparison of intracranial metastasis treatment using two radiosurgery systems: TrueBeam STx with VMAT and Gamma Knife Model 4C.

We compared treatment plan quality based on target coverage and normal brain tissue sparing for two intracranial stereotactic radiosurgery systems: TrueBeam STx using VMAT and Gamma Knife (GK). Ten patients with 24 tumors (seven with 1-2 and three with 4-6 ranging from 0.1 to 20.2 cc), previously treated with GK Model 4C (prescription doses ranging from 14-23 Gy), were re-planned for VMAT using Eclipse treatment planning system. Various photon beam energies and MLC leaf widths with and without jaw tracking were studied to achieve optimal plans. Plan qualities were assessed by target coverages using Paddick Conformity Index (PCI), normal-brain-tissue integral dose (Gy-cc) and sparing. In all cases critical structure dose criteria were met. The average PCI was 0.76±0.21 for VMAT and 0.46±0.20 for GK plans (p≤0.001), respectively. On average 81% reduction of 12 Gy normal-brain-tissue volumes was achieved by VMAT. The average integral dose ratio of GK to VMAT plans was 1.50±0.61 (p=0.006). VMAT was capable of producing higher quality treatment plans in terms of target coverage and normal brain tissue sparing than GK while using optimal beam geometries and optimization techniques.

Comparison of doses received by the hippocampus in patients treated with single isocenter- vs multiple isocenter-based stereotactic radiation therapy to the brain for multiple brain metastases.

To investigate the doses received by the hippocampus and normal brain tissue during a course of stereotactic radiation therapy using a single isocenter (SI)-based or multiple isocenter (MI)-based treatment planning in patients with less than 4 brain metastases. In total, 10 patients with magnetic resonance imaging (MRI) demonstrating 2-3 brain metastases were included in this retrospective study, and 2 sets of stereotactic intensity-modulated radiation therapy (IMRT) treatment plans (SI vs MI) were generated. The hippocampus was contoured on SPGR sequences, and doses received by the hippocampus and the brain were calculated and compared between the 2 treatment techniques. A total of 23 lesions in 10 patients were evaluated. The median tumor volume, the right hippocampus volume, and the left hippocampus volume were 3.15, 3.24, and 2.63mL, respectively. In comparing the 2 treatment plans, there was no difference in the planning target volume (PTV) coverage except in the tail for the dose-volume histogram (DVH) curve. The only statistically significant dosimetric parameter was the V100. All of the other measured dosimetric parameters including the V95, V99, and D100 were not significantly different between the 2 treatment planning techniques. None of the dosimetric parameters evaluated for the hippocampus revealed any statistically significant difference between the MI and SI plans. The total brain doses were slightly higher in the SI plans, especially in the lower dose region, although this difference was not statistically different. The use of SI-based treatment plan resulted in a 35% reduction in beam-on time. The use of SI treatments for patients with up to 3 brain metastases produces similar PTV coverage and similar normal tissue doses to the hippocampus and the brain when compared with MI plans. SI treatment planning should be considered in patients with multiple brain metastases undergoing stereotactic treatment.

Central nervous system metastasis in gynecologic cancer: symptom management, prognosis and palliative management strategies.

INTRODUCTION: CNS metastasis (CNSmet) with gynecologic malignancy (GM) is associated with poor prognosis and symptom burden. Two prognostic indices, the recursive partitioning analysis (RPA) and graded prognostic assessment (GPA), used in other solid tumors to guide intervention options were evaluated among GM patients. METHODS: Retrospective chart review was performed to identify patients with primary GM diagnosed with CNSmet from 2005-2014. RPA and GPA were applied and evaluated for goodness of fit. Long-term survivors (LTS) were those with survival time from CNSmet ≥9 months. RESULTS: 35 patients were identified with median age of 62 years (range, 41-78). The majority had ovarian cancer (54%). Median survival was 4.5 months (0.1-25.9), and median time from initial diagnosis was 2.6 years (0-19.6). Presenting symptoms varied but headache (57%) and altered mental status (23%) were most common. 37% had a solitary CNS lesion, 31% had 2-8, and 31% >8. 57% were treated with WBRT, 14% with stereotactic radiosurgery (SRS), and 20% with combinations of treatments, and 2 elected for hospice. 27% (9/33) of the patients were LTS. The GPA was not significantly associated with patient outcome (p=0.46). The RPA predicted time to death (p=.0010). CONCLUSION: Prognostic indices used to guide therapeutic interventions perform poorly in GM. Detection and aggressive symptom management are critical in maintaining QOL. Multidisciplinary consultation is critical to optimize outcomes and symptom control.

Quantitative assessment by measurement and modeling of mobile target elongation in cone-beam computed tomographic imaging.

The purpose of this study was to assess quantitatively elongation of mobile targets in cone-beam CT (CBCT) imaging by measurement and modeling. A mathematical model was derived that predicts the measured lengths of mobile targets and its dependence on target size and motion patterns in CBCT imaging. Three tissue-equivalent targets of differing sizes were inserted in an artificial thorax phantom to simulate lung lesions. Respiratory motion was mimicked with a mobile phantom that moves in one-dimension along the superior-inferior direction at a respiration frequency of 0.24 Hz for eight different amplitudes in the range 0-40 mm. A mathematical model was derived to quantify the variations in target lengths and its dependence on phantom motion parameters in CBCT. Predictions of the model were verified by measurement of the lengths of mobile targets in CBCT images. The model predicts that target lengths increased linearly with increase in speed and amplitude of phantom motion in CBCT. The measured lengths of mobile targets imaged with CBCT agreed with the calculated lengths within half-slice thickness spatial resolution. The maximal length of a mobile target was independent of the frequency and phase of motion. Elongation of mobile targets was similar in half-fan and full-fan CBCT for similar motion patterns, as long as the targets remained within the imaging view. Mobile targets elongated linearly with phantom speed and motion amplitude in CBCT imaging. The model introduced in this work assessed quantitatively the variation in target lengths induced by motion, which may be a useful tool to consider elongations of mobile targets in CBCT applications in diagnostic imaging and radiotherapy.

Dependency of planned dose perturbation (PDP) on the spatial resolution of MapCHECK 2 detectors.

The purpose of this study is to determine the dependency of the planned dose perturbation (PDP) algorithm (used in Sun Nuclear 3DVH software) on spatial resolution of the MapCHECK 2 detectors. In this study, ten brain (small target), ten brain (large target), ten prostate, and ten head-and-neck (H&N) cases were retrospectively selected for QA measurement. IMRT validation plans were delivered using the field-by-field technique with the MapCHECK 2 device. The measurements were performed using standard detector density (standard resolution; SR) and a doubled detector density (high resolution; HR) by merging regular with shifted measurements. SR and HR measurements were fed into the 3DVH software and ROI (region of interest), planning target volume (PTV), and organ at risk (OAR)) dose statistics (D95, Dmean, and Dmax) were determined for each. Differences of the dose statistics normalized to prescription dose for ROIs between original planning and PDP-perturbed planning were calculated for SR (ΔDSR) and HR (ΔDHR), and difference between ΔDSR and ΔDHR (ΔDSR-HR = ΔDSR - ΔDHR) was also calculated. In addition, 2D and 3D γ passing rates (GPRs) were determined for both resolutions, and a correlation between GPRs and ΔDSR or ΔDHR for PTV dose metrics was determined. No considerably high mean differences between ΔDSR and ΔDHR were found for almost all ROIs and plans (< 2%); however, |ΔDSR|, |ΔDHR|, and |ΔDSR-HR| for PTV were found to significantly increase as the PTV size decreased (e.g., PTV size < 5 cc). And statistically significant differences between SR and HR were observed for OARs proximal to targets in large brain target and H&N cases. As plan modulation represented by fractional MU/prescription dose (MU/cGy) became more complex, the 2D/3D GPRs tended to decrease; however, the modulation complexity did not make any noticeable distinctions in the DVH statistics of PTV between SR and HR, excluding the small brain cases whose PTVs were extremely small (PTV = 11.0 ± 10.1 cc). Moderate to strong negative correlations (-1 < r < -0.3) between GPRs and PTV dose metrics indicated that small clinical errors for PTV occur at the higher GPRs. In conclusion, doubling the detector density of the MapCHECK 2 device is recommended for small targets (i.e., PTV < 5 cc) and multiple targets with complex geometry with minimum setup error in the DVH-based plan evaluation.