231 Background: Recent studies have shown PVPs to be associated with diminished perioperative and postoperative complications compared to transurethral resection of the prostate (TURP) for benign prostatic hyperplasia (BPH). This is the first study to evaluate the timing of PVP intervention and post-treatment morbidity related to a combined regimen of DART and Pd-103 brachytherapy for treatment of prostate cancer. Methods: Between 12/05 and 04/20, 51 consecutive patients underwent Greenlight Laser (GLL) or Olympus Plasma Button (OPB) PVP after DART (median dose: 45 Gy) and before Pd-103 brachytherapy (median dose: 90 Gy). 27 patients received GLL PVP and 24 patients received OPB PVP. Peripheral seed loading designs were utilized to achieve optimal urethral sparing. The time from DART to PVP ranged from 1 to 81 days (median: 18 days). For 12 patients, the interval between DART and PVP was ≤7 days. The time from PVP to seed implant ranged from 0 to 55 days (median: 18 days). For 13 patients, the interval between PVP and implant was ≤7 days. American Urological Association (AUA) symptom scores were compiled prior to PVP and on the last post-brachytherapy follow-up. Post-implant follow-up ranged from 6 months to 15 years (median: 6.4 years). Results: No patient experienced post-implant urinary retention or incontinence. Morbidity was limited to RTOG grade 1-2 symptoms, with the exception of one patient who experienced protracted dysuria, which was identified to be secondary to a pre-existing prostate anomaly (steep urethral curvature). Only that patient required dilation for urethral stricture. AUA scores improved or remained the same in 43 of 51 patients. Only 1 patient of the remaining 8 experienced an increase in AUA > 8 points. Conclusions: In our experience, there have been remarkably few adverse urinary sequelae following Pd-103 implantation in patients with prior PVP and DART. In contrast to TURPs, PVPs are safe even with short intervals between DART and brachytherapy. Based upon these results, pre-implant PVP is preferred, rather than PVPs or TURPs in the post-implant setting.

Many scientists and regulators utilize the linear no-threshold (LNT) relationship to estimate the likelihood of carcinogenesis. The LNT model is incorrect and was adopted based upon false pretenses. The use of the model has been corrupted by many to claim that even the smallest ionizing radiation dose may initiate carcinogenesis. This claim has resulted in societal harm.

186 Background: Ferumoxytol (Feraheme) is a ferromagnetic nanoparticle with lymphotrophic biokinetics, delivered to lymph nodes by normal macrophages. MRI suppresses normal lymph nodes containing Feraheme. Objective is to validate safety and efficacy in finding lymph node positivity in prostate cancer (PCa). Methods: Nonrandomized prospective evaluation of 178 consecutive PCa patients (pts) at high risk for lymph node spread enrolled 2/13-3/15. All received IV Feraheme. 177 received 6/mg/kg over 20 min. One pt received 3 mg/kg infusion. T2 MEDIC and T2* sequence imaging of abdomen and pelvis, given 24 hours later. Images reviewed by 2 board certified radiologists with same interpretations, blinded to clinical and histo-path info (pre-MRI TNM stage/PSA/Gleason). Nodes were deemed abnormal if they did not suppress after Feraheme infusion (group 1, 94 patients). Nodes were deemed suspicious if suppressed and met usual size criteria with high signal intensity on DWI and decreased ADC map values and morphologic features (group 2, 84 pts). 83 group 1 pts had CT biopsies (77 pelvis, 6 retroperitoneum);11 pts had open PLND. 382 lymph nodes sampled. 76 group 2 patients had CT biopsies (73 pelvis, 3 retroperitoneum); 9 pts had open PLND. 340 lymph nodes sampled. Rad-path correlation was performed. Nodes were stained; reviewed by a single pathologist with no knowledge of MRI findings. Histo-path results for each node were cataloged for later MRI comparison. Results: 90 group 1 pts (96%) proved metastatic PCa; 4 pts (4%) were normal. 68 group 1 pts (77%) had malignant lymph nodes not meeting usual imaging criteria. 39 group 2 pts (47%) showed metastatic PCa; 46 pts (53%) were normal. One group 2 pt had an allergic reaction with hives; infusion ceased at 3mg/kg; pt treated to full resolution with 50 mg IV Benadryl. Conclusions: Feraheme can evaluate lymphatic dissemination of metastatic disease in PCa patients, with a lower limit of resolution of focal lymph node metastases of 2-3 mm. Better resolution gives implications for therapeutic radiation planning of newly diagnosed or recurrent/metastatic PCa. Toxicity was very acceptable at 6mg/kg. Feraheme may play a significant role as a lymphatic contrast agent in the early dissemination of lymphatic metastatic disease.

Cancer metastasis is a key event in tumor progression associated not only with mortality but also significant morbidity. Metastatic disease can promote end-organ dysfunction and even failure through mass effect compression of various vital organs including the spinal cord. In such cases, prompt medical attention is needed to restore neurological function, relieve pain, and prevent permanent damage. The three therapeutic approaches to managing metastatic spinal cord compression include corticosteroids, surgery, and radiation therapy. Although each may improve patients' symptoms, their combination has yielded the best outcome. In cancer patients with clinical suspicion of spinal cord compression, dexamethasone should be initiated followed by surgical decompression, when possible, and radiation. The latter becomes the preferred treatment in patients with inoperable disease.

Superior vena cava syndrome (SVCS) is a relatively common sequela of mediastinal malignancies and may cause significant patient distress. SVCS is a medical emergency if associated with laryngeal or cerebral edema. The etiologies and management of SVCS have evolved over time. Non-malignant SVCS is typically caused by infectious etiologies or by thrombus in the superior vena cava and can be managed with antibiotics or anti-coagulation therapy, respectively. Radiation therapy (RT) has long been a mainstay of treatment of malignant SVCS. Chemotherapy has also been used to manage SVCS. In the past 20 years, percutaneous stenting of the superior vena cava has emerged as a viable option for SVCS symptom palliation. RT and chemotherapy are still the only modalities that can provide curative treatment for underlying malignant etiologies of SVCS. The first experiences with treating SVCS with RT were reported in the 1970's, and several advances in RT delivery have subsequently occurred. Hypo-fractionated RT has the potential to be a more convenient therapy for patients and may provide equal or superior control of underlying malignancies. RT may be combined with stenting and/or chemotherapy to provide both immediate symptom palliation and long-term disease control. Clinicians should tailor therapy on a case-by-case basis. Multi-disciplinary care will maximize treatment expediency and efficacy.

Treatment related death (TRD) is the worst adverse event in chemotherapy and radiotherapy for patients with cancer, the reports for TRDs were sporadically. We aimed to study TRDs in non-small cell lung cancer (NSCLC) patients treated with concurrent chemoradiotherapy (CCRT), and determine whether high radiation dose and newer chemotherapy regimens were associated with the risk of TRD. Data from randomized clinical trials for locally advanced/unresectable NSCLC patients were analyzed. Eligible studies had to have at least one arm with CCRT. The primary endpoint was TRD. Pooled odds ratios (ORs) for TRDs were calculated. In this study, a total of fifty-three trials (8940 patients) were eligible. The pooled TRD rate (accounting for heterogeneity) was 1.44% for all patients. In 20 trials in which comparison of TRDs between CCRT and non-CCRT was possible, the OR (95% CI) of TRDs was 1.08 (0.70-1.66) (P = 0.71). Patients treated with third-generation chemotherapy and concurrent radiotherapy had an increase of TRDs compared to those with other regimens in CCRT (2.70% vs. 1.37%, OR = 1.50, 95% CI: 1.09-2.07, P = 0.008). No significant difference was found in TRDs between high (≥ 66 Gy) and low (< 66 Gy) radiation dose during CCRT (P = 0.605). Neither consolidation (P = 0.476) nor induction chemotherapy (P = 0.175) had significant effects with increased TRDs in this study. We concluded that CCRT is not significantly associated with the risk of TRD compared to non-CCRT. The third-generation chemotherapy regimens may be a risk factor with higher TRDs in CCRT, while high dose radiation is not significantly associated with more TRDs. This observation deserves further study.

The advent of modern radiation techniques, such as intensity modulated and stereotactic ablative radiation therapy, has permitted increasingly accurate delivery of radiation, with ability to shape distribution of dose specifically to the tumor. These techniques limit dose to surrounding normal tissue in an effort to reduce toxicity; however, despite such improvements, potentially serious side effects related to treatment may occur, requiring urgent management.

Background Preclinical studies on irradiated animals show that thrombocytopenia can play a role in radiation mortality, particularly in animals receiving minimal supportive care. These findings are consistent with anecdotal evidence from the atomic bombings, where bleeding complications were noted often in patients. Objective To evaluate the role of thrombocytopenia and hemorrhage in radiation-induced mortality, a review was conducted of publicly available pathology reports of patients who died following radiation exposure. Of the 42 reports identified with reasonably complete information, exposures resulted from nuclear detonation, contact with improperly disposed sources, radiotherapy, or industrial accidents. Results Consistent with animal data, a high incidence of bleeding was noted in the autopsy reports of the victims. Also presented is a review of animal model data on the use of various forms of thrombopoietin (TPO) as a treatment for hematopoietic acute radiation syndrome (ARS). Although animal studies suggested these approaches would increase platelet levels following lethal irradiation, their clinical development was halted due to lack of significant efficacy for chemotherapy-induced thrombocytopenia and safety concerns. Conclusion Because there is currently no approved treatment stockpiled for radiation-induced thrombocytopenia, second-generation TPO mimetics and other novel platelet-promoting agents should be developed for this indication.

Stereotactic body radiation therapy (SBRT) has been used for treatment of spinal cord compression. However, the treatment usually starts 1-2 days after simulation due to complicated planning and QA procedures. This work aims to study the feasibility of using a pre-QA’ed universal SBRT plan to treat the first fraction immediately after simulation for a 5-fraction regimen in emergency spine cases. A universal SBRT plan was created using intensity modulated radiation therapy (IMRT) to avoid the spinal cord for a virtual spinal target at T9-T10 level in an average-sized patient. The length of the target is 7 cm and the volume is 167 cm3. Target dose is 6 Gy with 95% dose coverage. The plan was retrospectively applied to 21 spinal SBRT patients (13 T-spine, 7 L-spine, and 1 C-spine) treated in our clinic, without changing any plan parameters except for adjusting the isocenter to spare the cord. Dose was calculated for the real targets and spinal organ at risk (SOAR, could be cord or caudal equine). The average, maximum and minimum of the mean dose to the real target were 5.97, 6.94, and 5.15 Gy, respectively. For SOARs, they were 3.63, 4.88, and 2.75 Gy, respectively. The average, maximum and minimum target coverage by 6 Gy was 53.9%, 90.4%, and 0%, respectively. The 0% happened in two patients with large size. However, the mean target dose still rendered 5.3 and 5.7 Gy, respectively for the 2 patients. The average, maximum and minimum dose to 10% SOAR was 4.77, 6.53, and 3.07 Gy, respectively. The maximum happened in a case with the SOAR tilted extremely. All cases were better than an AP or AP/PA plan. The ratio of mean dose to the cord and the target was 0.61. The ratio of the dose to 10% of cord and mean dose to the target was 0.80. While in PA or AP/PA plans, these ratios are usually 1. In addition, these cases can be planned in the remaining fractions to an ideal dose distribution to compensate the missing dose in the first fraction. Using a universal SBRT plan to treat the first fraction in cord compression may provide a potential safe strategy for urgent SBRT without compromise the tumor coverage and cord sparing. Future study may generate multiple pre-QA’ed plan templates to match each patient for more individualized planning.

Recognizing spinal cord dose limits in various fractionations is essential to ensure adequate dose for tumor control while minimizing the chance of radiation-induced myelopathy (RIM). This study aimed to determine the α/β ratio of the spinal cord and the cord dose limit in terms of BED50, the biological equivalent dose (BED) that induces 50 % chance of RIM, by fitting data collected from published animal and patient studies.

This study presents a MLC-based, 3D grid-therapy technique with characteristics of both 3D-conformal-radiotherapy and grid-therapy. It generates a brachytherapy-like dose distribution, with D50% of 20, 9.8, 5.4 and 2.9-Gy, for the spheres, target, 1cm-outershell and 2cm-outershell, respectively. It may provide a strategy to deliver ablative doses to large tumors safely.

Purpose: Volumetric Modulated Arc Therapy (VMAT) usually achieves higher conformity of radiation doses to targets and less delivery time than Intensity Modulated Radiation Therapy (IMRT). We hypothesized that VMAT will increase integral dose (ID) to patients which will decrease the count of white blood count (WBC) lymphocytes, and consequently has a subsequent impact on the immune system. The purpose of this study is to evaluate the ID to patients undergoing IMRT and VMAT for Head and Neck cancers and its impact on the immune system. Methods: As a pilot study, 30 head and neck patients who received 9-fields IMRT or 3-arcs Radip-Arcbased VMAT were included in this study. Ten of these patients who received the VMAT plans were re-planned using IMRT with the same objectives. ID was calculated for all cases. All patients also had a baseline WBC obtained prior to treatment, and 3 sets of labs drawn during the course of radiation treatment. Results: For the 10 re-planned patients, the mean ID was 13.3 Gy/voxel (range 10.2–17.5 Gy/voxel) for the 9-fields IMRT plans, and was 15.9 Gy/voxel (range 12.4-20.9 Gy/voxel) for the 3-Arc VMAT plan (p=0.01). The integral dose was significant correlated with reducing WBC count during RT even when controlling for concurrent chemotherapy (R square =0.56, p=0.008). Conclusion: Although VMAT can deliver higher radiation dose conformality to targets, this benefit is achieved generally at the cost of greater integral doses to normal tissue outside the planning target volume (PTV). Lower WBC counts during RT were associated with higher Integral doses even when controlling for concurrent chemotherapy. This study is ongoing in our Institution to exam the impact of integral doses and WBC on overall survival.

Preclinical and some anecdotal clinical studies have shown that immunotherapy and radiation therapy may have a synergy, and immune-modulation during radiation therapy may play an important role in cancer treatment. The immune system is adversely impacted during radiation therapy due to radiation dose delivered outside the target. We hypothesize that the integral dose (ID) is directly correlated with a decline in the immune system as represented by a decline in the WBC count. The purpose of this study is to investigate the correlation of ID to the white blood cells (WBC) as well as to the radiation therapy techniques, such as Intensity Modulated Radiation Therapy (IMRT) or Volumetric Modulated Arc Therapy (VMAT), As a pilot study, 30 head and neck patients who received IMRT or VMAT were included in this retrospective study. These patients had either 3 arcs of VMAT treatment or 9-fields of IMRT treatment. These patients had a baseline WBC obtained prior to treatment, and 3 sets of labs drawn during the course of radiation treatment. The WBC reduction due to radiation treatment was determined for each patient. The ID was also calculated for each patient. The ID, WBC reduction, and treatment technique (IMRT or VMAT), were compared and analyzed. The Integral dose has significant correlation with reduced WBC count during RT after controlling for concurrent chemotherapy (R square = 0.56, p = 0.008). When comparing the ID from 9-fields IMRT plans for and 3-Arc VMAT, the patients (n = 21) treated with VMAT plan had significantly higher ID compared to patients (n = 9) treated with IMRT plan. The mean ID was 16.4 Gy for VMAT and 13.0 Gy for IMRT with a p-value of 0.006. Lower WBC counts during RT were associated with higher Integral doses even when controlling for concurrent chemotherapy. Although IMRT and VMAT can deliver higher conformity of radiation doses to targets, however, these benefits are achieved generally at the cost of greater integral doses to normal tissue. This study is ongoing in our Institution to exam the impact of integral doses and white cell count on overall survival.

Low total lymphocyte count and lymphocyte to neutrophil ratio have been reported as poor prognostic indicators for multiple cancers at various stages. However, it is unknown whether the baseline complete blood count is associated with overall survival in patients with head and neck malignancies treated with radiation therapy. The objective of this study is to report the correlation that exists between baseline lymphocyte count and overall survival in patients with head and neck cancer treated with radiation based therapy. This is a retrospective analysis of 150 consecutive patients with non-metastatic Stage I-IV head and neck cancer who were treated with radiation therapy from November of 2009 to October of 2013. Pre-treatment complete blood count, demographic, and clinical variables were extracted from medical records and vital status was obtained by using the Social Security Death Index. Variables and outcomes were analyzed. Of the 150 patients reviewed, 104 had baseline complete blood counts (Median age 58, Male 74, Female 30). The median follow-up duration is 17.5 months. We performed 2 sequential analyses of the data. The initial analysis involved the first 82 patients and it was found that higher baseline lymphocyte count was significantly associated with lower mortality (HR: 0.93, p = 0.0443). The subsequent analysis involved 22 additional patients (n = 104). This was consistent with the findings from the initial analysis: i.e. higher baseline total lymphocyte count was associated with increased overall survival (HR 0.57, p = 0.0665). Other variables such as change in lymphocyte count (HR: 6*10-8, p = 0.749), baseline hemoglobin (HR: 0.87, p = 0.355), lymphocyte-to-neutrophil ratio (HR: 0.92, p = 0.306), age, gender, and race were not significantly associated with overall survival. There may be an association between the baseline lymphocyte count and overall survival in patients with head and neck cancers treated with radiation therapy. This result suggests immune function of each patient may be associated with overall survival. A study with larger sample size and longer follow-up is ongoing to validate this finding.

Peripheral blood cell counts have been reported as poor prognostic factors for cancer patients; however, it still remains unknown that whether they are important for patients treated with radiation therapy. We hypothesized that the overall survival (OS) may be associated with peripheral blood cell counts prior, during, and after radiation therapy in patients with non-small cell lung cancer (NSCLC). Patients with NSCLC treated with thoracic radiation, and with at least three peripheral blood tests including baseline (pre-treatment) and during-treatment data were eligible. Clinical factors including age, gender, clinical stage, concurrent chemotherapy, radiation information (total dose and fractions), total white blood cell, neutrophil, lymphocyte, hemoglobin, and platelet were extracted from the electronic medical records. Statistical analysis was conducted. The endpoint of this study is OS which was calculated using Kaplan-Meier method from the start of radiation therapy. Multivariate analysis was performed using Cox regression for the correlation between OS with clinical factors and components of the blood prior radiation as well as changes after radiation therapy. A P value of <.05 was considered statistically significant. A total of 105 consecutive patients treated between 2009 and 2013 were included in this study. The median (95% CI) age was 60 (59-64) years, and 68 (64.8%) patients were male. There were 5, 5, 47, and 48 patients for clinical stage I, II, III and IV, respectively. Twenty (19.0%) patients were treated with concurrent chemotherapy. The medians (95% CI) of radiation dose and fractions were 43.2 (38.9-46.0) Gy and 20 (18-22), respectively. The median duration of follow up was 23.1 months. The median (95% CI) OS was 13.3 (13.9-19.8) months. High baseline white blood cell and neutrophil counts were correlated with poor OS (P<.001; P=.009). Increasing neutrophils during radiation correlated with an improvement in OS (OR = 0.347, P=.037). Other variables such as hemoglobin, lymphocyte counts, and platelet were not significantly associated with OS before or after radiation therapy. High baseline white blood cell and neutrophil counts were related with poor OS in NSCLC patients receiving radiation therapy, possibly as a result of non-specific detrimental inflammatory response. Neutrophil rise after radiation initiation was associated with improved OS, possibly resulting in part from a directed inflammatory to the radiated carcinoma. This data suggests neutrophil may serve as a marker for treatment response. Further study is needed to validate these findings and the underlying mechanism.

* 8212 Old Georgetown Road, Bethesda, MD 20814. For correspondence contact the author at the above address, or email at [email protected]. (Manuscript accepted 16 June 2010)

OBJECTIVE Medical radiation exposure has increased sixfold since 1980 and is the largest controllable source of exposure. Many efforts have been devoted to reducing dose or eliminating unnecessary examinations but with limited success. The concern regarding nuclear terrorism has focused a large amount of attention on radioprotective drugs. The purpose of this article is twofold: to review the current concepts, potential, and limitations of chemical radioprotectants in reducing stochastic and deterministic effects and to assess the potential application to diagnostic and interventional medical radiation procedures. CONCLUSION There are a wide variety of chemical compounds that have been studied for radioprotective effects. Although there is promising research, chemical radioprotectants have not been shown to be very effective and, with one limited exception, are not the standard of care in medicine.

Efficient integration of functional genes is an essential prerequisite for successful gene delivery such as cell transfection, animal transgenesis, and gene therapy. Gene delivery strategies based on viral vectors are currently the most efficient. However, limited cargo capacity, host immune response, and the risk of insertional mutagenesis are limiting factors and of concern. Recently, several groups have used transposon-based approaches to deliver genes to a variety of cells. The piggyBac (pB) transposase in particular has been shown to be well suited for cell transfection and gene therapy approaches because of its flexibility for molecular modification, large cargo capacity, and high transposition activity. However, safety considerations regarding transposase gene insertions into host genomes have rarely been addressed. Here we report our results on engineering helper-independent pB plasmids. The single-plasmid gene delivery system carries both the piggyBac transposase (pBt) expression cassette as well as the transposon cargo flanked by terminal repeat element sequences. Improvements to the helper-independent structure were achieved by developing new plasmids in which the pBt gene is rendered inactive after excision of the transposon from the plasmid. As a consequence, potentially negative effects that may develop by the persistence of an active pBt gene posttransposition are eliminated. The results presented herein demonstrate that our helper-independent plasmids represent an important step in the development of safe and efficient gene delivery methods that should prove valuable in gene therapy and transgenic approaches.