Form Of Radiotherapy Research Articles

Abstract PS15-03: Breast complications in patients who received intraoperative radiation therapy compared to other forms of radiation therapy following breast conserving surgery

Abstract Introduction: Intraoperative radiation therapy (IORT) is a convenient treatment option for appropriate women with early stage breast cancer. Some patients undergoing IORT also need adjuvant whole breast radiation therapy due to adverse final pathologic features. Although there are various reports of the complication rates with patients undergoing IORT, comparisons with patients undergoing other forms of radiation therapy such as whole breast or accelerated partial breast radiation are sparse. Methods: A total of 293 patients underwent breast conserving surgery at the study institution between January 2016 and December 2019 for either ductal carcinoma in situ (DCIS) or invasive breast cancer. Three patients had bilateral breast cancer and one patient had a local recurrence having refused adjuvant treatment following breast conserving surgery, for a total of 297 treated breasts. 124 received whole breast radiation therapy, 70 did not receive radiation therapy, 47 received IORT alone, 15 received IORT and whole breast radiation therapy, 30 received accelerated partial breast radiation using external beam radiation (APBI-EB), and 9 received Ir-192 based high dose rate accelerated partial breast radiation (APBI-HDR). One patient with bilateral breast cancer did not complete whole breast radiation therapy to either breast. Complications included cellulitis, wound drainage, symptomatic seroma, delayed wound healing, and wet desquamation. Interventions included observation, antibiotics, wound packing, debridement, fluid aspiration, hydrogel dressings, and wound vacuums. Results: For the entire group, the incidence of wound complications was 20%. The risk of complications was 27.4% for those undergoing IORT (with or without whole breast radiation) compared to 18.3% for those not receiving IORT, which was not statistically different at the 5% significance level. For those who received both IORT and whole breast radiation, however, the proportion having complication was 53.3% versus 18.4% in the other groups. The difference was significant with a p-value 0.0032. Conclusion: Patients who undergo both IORT and whole breast radiation have an increased risk for wound complications. Citation Format: James Wheeler, Houman Vaghefi, Laura Morris, Fang Liu, Irina Sparks, Fiona Denham, Leonard Henry, Ashley Hardy, Meghan Schrock, Vanessa DePue, Leon Coody. Breast complications in patients who received intraoperative radiation therapy compared to other forms of radiation therapy following breast conserving surgery [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS15-03.

Robotic radical parametrectomy with pelvic lymphadenectomy: Technique and feasibility

Cervical cancer can be detected incidentally after simple hysterectomy carried out for benign gynecological conditions or preinvasive cervical lesions. The risk of recurrence is high, and survival is poor in the absence of further treatment in the form of radiation therapy or radical parametrectomy. Though both forms of treatment result in similar survival, surgery has the advantage to stage the disease and guide the need for adjuvant therapy and also avoids the radiation-associated complications. Though traditionally performed by laparotomy, laparoscopic and robotic approaches have been found to be feasible and safe for this complex procedure.

Metastasis to the Central Nervous System.

Management of metastasis to the central nervous system (CNS) has evolved, and molecular characterization of metastatic disease is now routinely done. Targeted therapies, once few in number with limited penetration into the CNS, have multiplied in number and increased in CNS coverage. This article addresses recent advances in the evaluation and clinical management of patients with CNS metastasis. Metastasis of cancer to the CNS can be diagnosed and characterized with novel techniques, including molecular analyses of the spinal fluid, so-called liquid biopsies. Resected parenchymal CNS metastases are now routinely subjected to genomic sequencing. For patients with CNS metastases displaying targetable mutations, a wide variety of treatment options are available, including deferral of radiation therapy in favor of a trial of an orally bioavailable targeted therapy or immunotherapy. For patients without a molecularly targetable lesion, local treatment in the form of radiation therapy, now most often stereotactic radiosurgery, is supplanting untargeted whole-brain radiation therapy. Technologic advances in diagnosis and management have resulted in new diagnostic and therapeutic approaches to patients with metastasis to the CNS, with resulting improvements in progression-free and overall survival.

Folate hydrolase-1 (FOLH1) is a novel target for antibody-based brachytherapy in Merkel cell carcinoma.

BackgroundsFolate Hydrolase‐1 (FOLH1; PSMA) is a type II transmembrane protein, luminally expressed by solid tumour neo‐vasculature. Monoclonal antibody (mAb), J591, is a vehicle for mAb‐based brachytherapy in FOLH1+ cancers. Brachytherapy is a form of radiotherapy that involves placing a radioactive material a short distance from the target tissue (e.g., on the skin or internally); brachytherapy is commonly accomplished with the use of catheters, needles, metal seeds and antibody or small peptide conjugates. Herein, FOLH1 expression in primary (p) and metastatic (m) Merkel cell carcinoma (MCC) is characterized to determine its targeting potential for J591‐brachytherapy.Materials & MethodsParaffin sections from pMCC and mMCC were evaluated by immunohistochemistry for FOLH1. Monte Carlo simulation was performed using the physical properties of conjugated radioisotope lutetium‐177. Kaplan–Meier survival curves were calculated based on patient outcome data and FOLH1 expression.ResultsEighty‐one MCC tumours were evaluated. 67% (54/81) of all cases, 77% (24/31) pMCC and 60% (30/50) mMCC tumours were FOLH1+. Monte Carlo simulation showed highly localized ionizing tracks of electrons emitted from the targeted neo‐vessel. 42% (34/81) of patients with FOLH1+/− MCC had available survival data for analysis. No significant differences in our limited data set were detected based on FOLH1 status (p = 0.4718; p = 0.6470), staining intensity score (p = 0.6966; p = 0.9841) or by grouping staining intensity scores (− and + vs. ++, +++, +++) (p = 0.8022; p = 0.8496) for MCC‐specific survival or recurrence free survival, respectively.ConclusionsWe report the first evidence of prevalent FOLH1 expression within MCC‐associated neo‐vessels, in 60‐77% of patients in a large MCC cohort. Given this data, and the need for alternatives to immune therapies it is appropriate to explore the safety and efficacy of FOLH1‐targeted brachytherapy for MCC. What's already known about this topic? We report the first evidence of prevalent folate hydrolase‐1 (FOLH1; also known as prostate‐specific membrane antigen) expression within MCC‐associated neovessels. What does this study add? Herein, FOLH1 expression in Merkel cell carcinoma neovasculature is validated, and the therapeutic mechanism of specific, systemic targeting of disseminated disease with antibody‐based brachytherapy, is defined.

Current Management of Craniopharyngiomas

This paper reviews the current management of craniopharyngioma tumors with a focus on surgical treatment options. Advances in transnasal endoscopic skull base surgery and proton therapy have altered the management options available for this challenging condition. Craniopharyngiomas are benign suprasellar tumors that originate from Rathke’s pouch. These complex lesions may cause major neurologic, endocrine, and visual deficits. Treatment modalities include endoscopic transnasal versus open transcranial surgery to achieve gross total or subtotal resection. Various forms of radiation therapy are often integral to comprehensive management of craniopharyngiomas. This article reviews current treatment modalities and surgical risks, highlighting differences between endoscopic versus transcranial surgical approaches.

The influence of the α/β ratio on treatment time iso-effect relationships in the central nervous system

Purpose: To investigate the influence of changes in α/β ratio (range 1.5–3 Gy) on iso-effective doses, with varying treatment time, in spinal cord and central nervous system tissues with comparable radio-sensitivity. It is important to establish if an α/β ratio of 2 Gy, the accepted norm for neuro-oncology iso-effect estimations, can be used.Methods: The rat spinal cord irradiation data of Pop et al. provided ED50 values for radiation myelopathy for treatment times that varied from minutes to ∼6 days. Analysis using biphasic repair kinetics, allowing for variable dose-rates, provided the best fit with repair half-times of 0.19 and 2.16 hr, each providing ∼50% of overall repair; with an α/β ratio 2.47 Gy (CI 1.5–3.95 Gy). Using the above data set, graphical methods were used to investigate changes in the repair parameters for differing fixed α/β ratios between 1.5 and 3.0 Gy. Two different intermittent dose delivery equations were used to evaluate the implications in a radiosurgery setting.Results: Changes in the α/β ratio (1.5–3.0 Gy) have a minor effect on equivalent doses for radiation myelopathy for treatment durations of a few hours. Changing the α/β value from 2 Gy to 2.47 Gy, modified equivalent single doses by < 1% when overall treatment times ranged from 0.1 to 5.0 hr. Significant changes were only found for treatment times longer than 5–10 hr. These two α/β ratios were also compared in a practical radiosurgery situation, using two different models for estimating BED, again there was no significant loss of accuracy.Conclusions: It is reasonable to use an α/β ratio of 2 Gy for CNS tissue, with the same repair half-times as published in the original publication by Pop et al., in situations where the assessment of the BED in radiosurgery is used with other form of radiotherapy. In radiosurgery, the variation in BED with treatment duration (for a fixed physical dose) is very similar, but absolute BED values depend on the α/β value. In radiosurgery, clinical recommendations obtained using BED calculations using the originally proposed α/β ratio of 2.47 Gy are still appropriate. For calculations involving a combination of radiosurgery and other modalities, such as fractionated radiotherapy, it would be appropriate in all cases to apply a value of 2 Gy, the accepted norm in neuro-oncology, without significant loss of accuracy in the radio-surgical component. This may have important applications in retreatment situations.

Uveal melanoma.

Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. UMs are usually initiated by a mutation in GNAQ or GNA11, unlike cutaneous melanomas, which usually harbour a BRAF or NRAS mutation. The annual incidence in Europe and the USA is ~6 per million population per year. Risk factors include fair skin, light-coloured eyes, congenital ocular melanocytosis, ocular melanocytoma and the BAP1-tumour predisposition syndrome. Ocular treatment aims at preserving the eye and useful vision and, if possible, preventing metastases. Enucleation has largely been superseded by various forms of radiotherapy, phototherapy and local tumour resection, often administered in combination. Ocular outcomes are best with small tumours not extending close to the optic disc and/or fovea. Almost 50% of patients develop metastatic disease, which usually involves the liver, and is usually fatal within 1 year. Although UM metastases are less responsive than cutaneous melanoma to chemotherapy or immune checkpoint inhibitors, encouraging results have been reported with partial hepatectomy for solitary metastases, with percutaneous hepatic perfusion with melphalan or with tebentafusp. Better insight into tumour immunology and metabolism may lead to new treatments.

ACR-ASTRO Practice Parameter for the Performance of Proton Beam Radiation Therapy.

The American College of Radiology (ACR) and the American Society for Radiation Oncology (ASTRO) have jointly developed the following practice parameter for proton beam radiation therapy. Proton radiotherapy is the application of a high-energy proton beam to a patient in a clinical setting with therapeutic intent. Proton radiotherapy may permit improved therapeutic ratios with lower doses to sensitive normal structures and greater dose to target tumor tissues. A literature search was performed to identify published articles regarding clinical outcomes, reviews, quality assurance methodologies, and guidelines and standards for proton radiation therapy. Selected articles are referenced in the text. The following recommendations are based on firsthand experiences of multiple clinical authorities who employ proton therapy and have been peer reviewed by experts at different practicing institutions. This practice parameter is developed to serve as a tool in the appropriate application of this evolving technology in the care of cancer patients or other patients with conditions where radiation therapy is indicated. It addresses clinical implementation of proton radiation therapy, including personnel qualifications, quality assurance standards, indications, and suggested documentation. This practice parameter is a tool to guide technical use of proton therapy and does not assess the relative clinical indication of proton radiotherapy when compared with other forms of radiotherapy, but to focus on the best practices required to deliver proton therapy safely and effectively, when clinically indicated. Costs of proton treatments are high, and the economic costs of proton radiotherapy may also need to be considered.

Comparative evaluation of image registration methods with different interest regions in lung cancer radiotherapy

BackgroundLung cancer is a leading cause of morbidity and mortality worldwide. Radiotherapy for lung cancer is beneficial in both the radical and palliative settings, and technologic advances in recent years now afford an opportunity for this treatment to be more targeted than ever before. Although the delivery of more accurate forms of radiotherapy has minimized the risks of side-effects, how to utilize this treatment to optimize outcomes remains questionable. This study aimed to evaluate the accuracy of cone beam computed tomography (CBCT) image registration used in image-guided radiotherapy, providing reasonable guidance for clinic application of CBCT in lung cancer.MethodsA total of 53 patients with lung carcinoma including 34 central and 19 peripheral lesions were collected in this study. Varian-IX linear accelerator on-board imaging (OBI) system was used to acquire CBCT scans in three-dimensional (3D) conformal radiotherapy before delivery. Different regions (whole lung/target/vertebrae/ipsilateral structure) were manually registered, and the position deviation and the registration time were analyzed.ResultsIt was suggested that 34 cases belonged to central type and 19 cases belonged to peripheral type. The volume of left lung and right lung was 1242.98 ± 452.46 cc, 1689.69 ± 574.31 cc, respectively. Tumor size was 6.65 ± 3.87 cm in diameter, and 129.67 ± 136.48 cc in volume. The percentage of left lung and right lung was 6.17 ± 1.24%, 4.74 ± 0.38%, respectively. The position deviation value and absolute value of image registration methods of X, Y and Z axis were not significant (P > 0.05). However, registration time (s) between whole lung registration group, tumor registration group, vertebral body registration group, affected lung registration group, and artificial registration group, was 3.651 ± 0.867 s, 1.144 ± 0.129 s, 1.226 ± 0.126 s, 2.081 ± 0.427 s, 179.491 ± 71.975 s, respectively. The differences were significant (P < 0.05). The registration differences between small tumor group and large tumor group were not statistically significant (P > 0.05).ConclusionThe automatic image matching of OBI is accuracy and high reliability in recognition of offset error. Registering body or ipsilateral structure is recommended to be used in CBCT for lung cancer.

Emerging Translational Opportunities in Comparative Oncology With Companion Canine Cancers: Radiation Oncology.

It is estimated that more than 6 million pet dogs are diagnosed with cancer annually in the USA. Both primary care and specialist veterinarians are frequently called upon to provide clinical care that improves the quality and/or quantity of life for affected animals. Because these cancers develop spontaneously in animals that often share the same environment as their owners, have intact immune systems and are of similar size to humans, and because the diagnostic tests and treatments for these cancers are similar to those used for management of human cancers, canine cancer provides an opportunity for research that simultaneously helps improve both canine and human health care. This is especially true in the field of radiation oncology, for which there is a rich and continually evolving history of learning from the careful study of pet dogs undergoing various forms of radiotherapy. The purpose of this review article is to inform readers of the potential utility and limitations of using dogs in that manner; the peer-reviewed literature will be critically reviewed, and current research efforts will be discussed. The article concludes with a look toward promising future directions and applications of this pet dog “model.”

Major limits of dosimetrically determined activities in advanced differentiated thyroid carcinoma.

The 2013/59 EURATOM directive defines all nuclear medicine applications for therapeutic purpose as a form of radiotherapy and underlines the need of both justification and optimization of these procedures, including radioactive iodine therapy (RAIT) with [131I] for metastatic differentiated thyroid cancer (DTC). In metastatic DTC, optimal activity to be administered to achieve the best response rate with limited toxicity is still a matter of debate and international guidelines do not provide univocal recommendations on the preferable use of empiric versus a dosimetry-based approach in these patients. The purpose of this literature review is to describe the possible limits of dosimetry in RAIT planning according to methodological aspects, tumoral heterogeneity and to report clinical data on the impact on patients' outcome of different approaches. Due to the lack of standardized dosimetry protocols and clinical data assessing the superiority of a dosimetry-based vs an empiric approach in these patients, there is a need of standardisation and prospective, properly conducted studies to validate and to assess the best approach.

The impact of age on the outcome of patients treated with radiotherapy for mucoepidermoid carcinoma (MEC) of the salivary glands in the head and neck: A 15-year single-center experience

IntroductionData regarding treatment and survival outcome of patients with mucoepidermoid carcinoma of the head and neck are limited to case reports and case series. As a consequence of lacking evidence, treatment guidelines do not exist. We aimed to analyze the effect of modern radiotherapy in form of intensity modulated radiotherapy (IMRT) either with simultaneously integrated boost or carbon ion boost on local control and survival for a relatively large patient collective. Materials and methodsPatient records of 62 consecutive patients treated with postoperative (n = 53, 85%) or definitive (n = 9, 15%) radiotherapy between 2004 and 2019 were analyzed retrospectively. Kaplan-Meier estimates for overall survival (OS), distant progression-free survival (PFS), local control (LC) and locoregional control (LRC) were statistically calculated and prognostic factors were identified using the log-rank test. Toxicity was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE). ResultsThe median follow-up was 47 months (range, 4–188 months). The 3-year OS, DPFS, LC and LRC, estimated by Kaplan-Meier curves, were 82%, 87%, 89% and 92%, the estimated 5-year OS, DPFS, LC and LRC were 78%, 87%, 84% and 88%, respectively. In univariate analysis, age >56 years (vs. age ≤56 years) was identified as the only independent negative prognostic factor for decreased OS (HR = 1.078; 95%-CI = 1.029–1.130; p = 0.001), DPFS (HR = 1.055; 95%-CI = 1.000–1.114; p = 0.051) and LC (HR = 1.087; 95%-CI = 1.022–1.157; p = 0.008). Treatment was well tolerated without any grade ≥4 toxicity. Acute and late grade 3 toxicities were rare with 16% acute (n = 10) and 13% late toxicities (n = 8). ConclusionRadiotherapy with intensity modulated radiotherapy including either simultaneously integrated photon boost or active raster-scanning carbon ion boost for mucoepidermoid carcinomas of the head and neck resulted in excellent survival outcome and locoregional control with moderate toxicity. However, patients older than 56 years seem to have a disadvantage in all calculated endpoints (OS, DPFS, LRC) due to frequent local and distant relapses. Condensed abstractModern radiotherapy with intensity modulated radiotherapy including either a simultaneously integrated photon boost or carbon ion boost for mucoepidermoid carcinoma results in excellent survival outcome and locoregional control with moderate toxicity. The 5-year OS, DPFS, LC and LRC, estimated by Kaplan-Meier curves, were 89%, 75%, 84% and 80%, respectively. Patients older than 56 years seem to have a disadvantage in all calculated endpoints (OS, DPFS, LRC).

Neutron Chareacterization of BNCT Water Phantom Based on 30 MeV Cyclotron Using PHITS Computational Code

Cancer is the second leading cause of death globally and was responsible for 8,8 million deaths in 2015. Approximately 70% of deaths from cancer occur in low- and middle-income countries. The war on cancer has been fought with three tools – surgery (cut), radiation therapy (burn) including radiotherapy and bracytherapy, and also chemotherapy (poison). Cancer therapy has increased life expectancy of patients but each treatment modality has its own effects, complications and toxicity. Moreover we have found a new effective method to fight cancer, that is, Boron Neutron Capture Therapy (BNCT). Boron Neutron Capture Therapy (BNCT) has for many decades been advocated as an innovative form of radiotherapy that, in principle, has the potential to be the ideal form of treatment for many types of cancers. This research’s aim is the characterising neutron of BNCT water phantom based on 30 MeV cyclotron using PHITS computational code. The result from the simulation is that thickness of the water phantom, related to flux neutron.

GPU Accelerated Stochastic Origin Ensemble Method With List-Mode Data for Compton Camera Imaging in Proton Therapy

Proton beam therapy has the advantages over other forms of radiation therapy because it does less damage to healthy tissue while treating cancerous tissue. These advantages arise from the high dose deposition at the end of the proton beam which is known as the Bragg peak. This paper proposes a new architecture for graphics processing unit (GPU)-accelerated stochastic origin ensemble (SOE) algorithm, eventually achieves a great acceleration and allows to reconstruct images of the gamma radiation produced by proton beam in real time. The object of this paper is to improve the run time of SOE algorithm for improving the accuracy of the proton therapy. In previous studies, it is difficult to reconstruct images of prompt gamma (PG) ray in real time in proton therapy. After analyzing the structure of the SOE algorithm, we correspond each gamma ray detected by Compton camera (CC) to each thread in GPU, initialize the origin cones in GPU, and use data structures which are suitable for parallelization, shared memory, and random number lists to speed up parallel program. To evaluate the proposed method, we use the parallel SOE algorithm to reconstruct the sources with the CC imaging system, which is simulated by Geant4. The parallel program on the GPU eventually achieves a 25× speedup over serial CPU run, reconstructing images of gamma radiation in 0.4 s. In the end, we also accelerate the Monte Carlo-based back projection (MC-BP) algorithm, the parallel program achieves a 79× speedup over serial CPU run.

Primary cryotherapy for localised or locally advanced prostate cancer

Background Traditionally, radical prostatectomy and radiotherapy with or without androgen deprivation therapy have been the main treatment options to attempt to cure men with localised or locally advanced prostate cancer. Cryotherapy is an alternative option for treatment of prostate cancer that involves freezing of the whole prostate (whole gland therapy) or only the cancer (focal therapy), but it is unclear how effective this is in comparison to other treatments. Objectives To assess the effects of cryotherapy (whole gland or focal) compared with other interventions for primary treatment of clinically localised (cT1-T2) or locally-advanced (cT3) non-metastatic prostate cancer. Search methods We updated a previously published Cochrane Review by performing a comprehensive search of multiple databases (CENTRAL, MEDLINE, EMBASE), clinical trial registries (ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform) and a grey literature repository (Grey Literature Report) up to 6 March 2018. We also searched the reference lists of other relevant publications and conference proceedings. We applied no language restrictions. Selection criteria We included randomised or quasi-randomised trials comparing cryotherapy to other interventions for the primary treatment of prostate cancer. Data collection and analysis Two independent reviewers screened the literature, extracted data, and assessed risk of bias. We performed statistical analyses using a random-effects model and interpreted them according to the Cochrane Handbook for Systematic Reviews of Interventions. We rated the quality of evidence (QoE) according to the GRADE approach. Main results We included only one comparison of whole gland cryotherapy versus external beam radiotherapy, which was informed by two trials with a total of 307 randomised participants. The median age of the included studies was around 70 years. The median follow-up of included studies ranged from 100 to 105 months.Primary outcomes: we are uncertain about the effect of whole gland cryotherapy compared to radiation therapy on time to death from prostate cancer; hazard ratio (HR) of 1.00 (95% confidence interval (CI) 0.11 to 9.45; 2 trials, 293 participants; very low QoE); this would correspond to zero fewer death from prostate cancer per 1000 men (95% CI 85 fewer to 520 more). We are equally uncertain about the effect of quality of life-related urinary function and bowel function (QoL) at 36 months using the UCLA-Prostate Cancer Index score for which higher values (range: 0 to 100) reflect better quality of life using minimal clinically important differences (MCID) of 8 and 7 points, respectively; mean difference (MD) of 4.4 (95% CI -6.5 to 15.3) and 4.0 (95% CI -73.96 to 81.96), respectively (1 trial, 195 participants; very low QoE). We are also uncertain about sexual function-related QoL using a MCID of 8 points; MD of -20.7 (95% CI -36.29 to -5.11; 1 trial, 195 participants; very low QoE). Lastly, we are uncertain of the risk for major adverse events; risk ratio (RR): 0.91 (95% CI 0.47 to 1.78; 2 trials, 293 participants; very low QoE); this corresponds to 10 fewer major adverse events per 1000 men (95% CI 58 fewer to 86 more). Secondary outcomes we are very uncertain about the effects of cryotherapy on time to death from any cause (HR 0.99, 95% CI 0.05 to 18.79; 2 trials, 293 participants; very low QoE), and time to biochemical failure (HR 2.15, 95% CI 0.07 to 62.12; 2 trials, 293 participants; very low QoE). Rates of secondary interventions for treatment failure and minor adverse events were either not reported in the trials, or the data could not be used for analyses.We found no trials that compared whole gland cryotherapy or focal cryotherapy to other treatment forms such as radical surgery, active surveillance, watchful waiting or other forms of radiotherapy. Authors' conclusions Based on very low quality evidence, primary whole gland cryotherapy has uncertain effects on oncologic outcomes, QoL, and major adverse events compared to external beam radiotherapy. Reasons for downgrading the QoE included serious study limitations, indirectness due to the use of lower doses of radiation in the comparison group than currently recommended, and serious or very serious imprecision.

Seizure prevalence, contributing factors, and prognostic factors in patients with leptomeningeal disease

BackgroundTo determine seizure prevalence and contributing factors in patients with leptomeningeal disease (LMD). MethodsAuthors performed a retrospective review of 79 consecutive patients with a diagnosis of LMD. Associations between categorical variables were assessed using Chi-Square tests or Fisher's Exact tests. Survival was plotted with Kaplan Meier curves. Variables with a log-rank p-value of <0.20 were entered into a Cox Proportional Hazard regression analysis. ResultsSeizure prevalence in those with and without brain metastases was 22%. Of those who seized, 65% were admitted for this at least once while only one patient required intubation. Primary malignancy, type or route of chemotherapy administration, form of radiation therapy (craniospinal, focal, or whole brain), surgical treatment, location of LMD, and number of brain metastases did not influence seizure development. Only 13% of patients who never had seizures were on a prophylactic AED (anti-epileptic drug). In patients who had brain metastasis, there was no significant difference in prevalence of seizure before versus after LMD diagnosis suggesting that LMD does not significantly increase the risk of seizure compared to brain metastasis alone. A multivariate analysis revealed that while males trended toward inferior survival, only performance status and treatment with systemic chemotherapy showed a significant association with survival. Median survival time of patients after LMD diagnosis was four months. ConclusionThe prevalence of seizure in LMD patients is 22%. There were no statistically significant predisposing factors to seizure development. ECOG and use of systemic chemotherapy were found to be significant prognostic factors.

NCMP-25. SEIZURE INCIDENCE AND CONTRIBUTING FACTORS IN PATIENTS WITH LEPTOMENINGEAL DISEASE

Seizures are a well-known complication of CNS malignancy, however there is little in the literature regarding leptomeningeal disease (LMD) and seizures. The incidence of seizures is unknown in this specific cohort as is the use or potential benefit of preventative anti-seizure medications (AEDs). Additionally, factors that might predispose LMD patients to seize or affect their survival are largely unexplored. Retrospective review of 79 patients with a diagnosis of LMD treated at a single institution from August 2012 to August 2017. Associations between categorical variables were tested using Fisher’s Exact tests. Differences in survival between groups were plotted with Kaplan Meier curves and tested using log-rank tests. All analyses were performed using SAS software. Seizure incidence in those with and without brain metastases was 22%. Of those who seized, 65% were admitted for this at least once while only one patient required intubation. Primary malignancy, type or route of chemotherapy administration, form of radiation therapy (craniospinal, focal, or whole brain), and number of brain metastases did not influence seizure development. Only 8% of patients who never had seizures were on a prophylactic AED. In patients who had brain metastasis, there was no significant difference in incidence of seizure before vs after LMD diagnosis suggesting that LMD does not significantly increase the risk of seizure compared to brain metastasis alone. There was additionally no significant difference in survival time between patients who did or did not seize. Median survival time of patients after LMD diagnosis was 4 months. The incidence of seizure in LMD patients is 22%. There were no statistically significant predisposing factors to seizure development. Additionally, the development of seizures does not affect survival in patients with LMD.

3-D Image-Based Dosimetry in Radionuclide Therapy

Radionuclide therapy is the use of radioactive drugs for internal radiotherapy, mainly for the treatment of metastatic disease. As opposed to systemic cancer therapies in general, the use of radioactively labeled drugs results not only in a targeted therapy but also the possibility of imaging the distribution of the drug during therapy. From such images, the absorbed doses delivered to tumors and organs at risk can be calculated. Calculation of the absorbed dose from 3-D images such as single-photon emission computed tomography (SPECT)/CT, and in some cases positron emission tomography (PET)/CT, relies on image-based activity quantification. Quantification is accomplished by modeling the physics involved in the image-formation process, and applying image-processing methods. From a time-sequence of such quantitative images, the absorbed doses are then calculated. Although individual-patient dosimetry is a standard component of other forms of radiotherapy, it is still overlooked in the majority of radionuclide therapies. In this review, we summarize the physical and technical problems that need to be addressed in image-based dosimetry. The focus is on SPECT, since most of the radionuclides used are single-photon emitters, although the use of PET is also discussed. Practical issues of relevance for the practical implementation of personalized dosimetry in radionuclide therapy are also highlighted.

Efficacy and Toxicity of Stereotactic Body Radiation Therapy for Localized Prostate Cancer: A Ten-Year Study

Stereotactic body radiation therapy (SBRT) is a newer treatment option for localized prostate cancer (PCa), with recent studies demonstrating excellent control rates and low toxicity with short to intermediate follow-up. Longer term patient outcomes demonstrating efficacy and safety, however, have not yet been previously reported. In this present study, we report 10-year outcomes for prostate SBRT in 515 patients. Consecutively treated patients (n=515) between 2006-2009 were evaluated (median FU = 108 mos). There were 324, 153 and 38 low-, intermediate- and high-risk patients by NCCN criteria. Patients received Robotic SBRT (35-36.25 Gy in 5 fractions on consecutive days). The dose was defined to cover 95% of the Planning Treatment Volume, which was a 5 mm expansion (3mm posteriorly) of the prostate and proximal seminal vesicles. 95% of the prostate was covered by 38.5-40 Gy. Real time tracking of fiducial seeds was employed. 102 patients received ADT for up to 6 months. For the entire patient cohort, 10-year biochemical recurrence free survival (bRFS) was 93, 81 and 66% for low-risk, intermediate-risk, and high-risk patients. Biopsy proven local failure was found in 2, 6 and 10%, respectively. Favorable intermediate-risk patients (Gleason 3+4=7 with no other intermediate-risk factors, or Gleason 3+3 = 6 with only one intermediate-risk factor) had excellent outcomes, with no significant difference compared to low-risk patients (10y DFS 89 vs 93%, P=0.3). Unfavorable intermediate-risk patients had outcomes similar to high-risk patients (10y bDFS of 63 vs 66%, P=0.8). PSA and Gleason score were the only significant factors predicting for bRFS on multivariate analysis (P<0.002) with dose, ADT not significant. Toxicity was overall mild. There was significantly higher late G2-3 GU toxicity with 36.25 Gy compared to 35 Gy (14.6 vs 8.2%, P=0.04), but no difference in G2 GI toxicity. Mean EPIC QOL urinary and bowel domains for all patients declined during the first 3 months and then returned to baseline. Mean sexual QOL scores declined by 40% at 10 years In conclusion, prostate SBRT continues to demonstrate excellent biochemical and local control rates with low toxicity and excellent QOL with now 10 years of follow up. Our results are at least as favorable as other forms of radiation therapy. We continue to find 35 Gy to be as effective as 36.25 Gy, with significantly lower GU toxicity, suggesting 35 Gy may be a preferable dose for patients with low- and favorable intermediate-risk disease. Long-term results of prospective studies are needed to validate our findings. For higher risk patients, the use of ADT failed to demonstrate improvement in long-term disease control. Given that most SBRT failures were not local, we hypothesize that dose escalation will not translate to improved bFRS, and strategies to reduce systemic failures should be explored.

Stereotactic body radiation therapy in primary hepatocellular carcinoma: current status and future directions.

Stereotactic body radiation therapy (SBRT) is a form of radiation therapy that has been used in the treatment of primary hepatocellular carcinoma (HCC) over the past decade. To evaluate the clinical efficacy of SBRT in primary HCC, a literature search was conducted to identify original research articles published from January 2000 through January 2018 in PubMed on SBRT in HCC. All relevant studies published from 2004 to 2018 were included. Prospective studies demonstrated 2-year local control (LC) rates ranging from 64-95% and overall survival (OS) rates ranging from 34% (2-year) to 65% (3-year). Retrospective studies demonstrated 2-year LC rates of 44-90% and 2-year OS rates of 24-67%. Reported toxicities in primary HCC patients vary but SBRT appears to be relatively well tolerated. Studies comparing SBRT to radiofrequency ablation (RFA) are few, but they suggest SBRT may be more effective than RFA in specific primary HCC populations. Additionally, SBRT appears to increase the efficacy of both transarterial chemoembolization (TACE) and sorafenib in selected primary HCC populations.