Showing papers in "Advances in radiation oncology in 2016"

Comparison of outcomes between SBRT, yttrium-90 radioembolization, transarterial chemoembolization, and radiofrequency ablation as bridge to transplant for hepatocellular carcinoma.

Abstract: Purpose To evaluate and compare outcome of stereotactic body radiation therapy (SBRT), yttrium-90 radioembolization, radiofrequency ablation (RFA), or transarterial chemoembolization (TACE) as bridge to liver transplant (LT) in patients with hepatocellular carcinoma. Methods and materials We retrospectively reviewed patients treated at our institution with SBRT, TACE, RFA, or yttrium-90 as bridge to LT between 2006 and 2013. We analyzed radiologic and pathologic response and rate of failure after bridge therapy. Toxicities were reported using Common Terminology Criteria for Adverse Events, 4.0. Kaplan-Meier method was used to calculate disease-free survival (DFS) and overall survival after LT. Results Sixty patients with a median age 57.5 years (range, 44-70) met inclusion criteria. Thirty-one patients (50.7%) had hepatitis C cirrhosis, 14 (23%) alcoholic cirrhosis, and 8 (13%) nonalcoholic steatohepatitis cirrhosis. Patients received a total of 79 bridge therapies: SBRT (n = 24), TACE (n = 37), RFA (n = 9), and Y90 (n = 9). Complete response (CR) was 25% for TACE, 8.6% for SBRT, 22% for RFA, and 33% for Y90. Grade 3 or 4 acute toxicity occurred following TACE (n = 4) and RFA (n = 2). Transplant occurred at a median of 7.4 months after bridge therapy. Pathological response among 57 patients was 100% necrosis (n = 23, 40%), >50% necrosis (n = 20, 35%), Conclusion All bridge therapies demonstrated good pathological response and DFS after LT. SBRT and Y90 demonstrated significantly less grade ≥3 acute toxicity. Choice of optimal modality depends on tumor size, pretreatment bilirubin level, Child-Pugh status, and patient preference. Such a decision is best made at a multidisciplinary tumor board as is done at our institution.

Radiation-induced erectile dysfunction: Recent advances and future directions

Abstract: Prostate cancer is one of the most prevalent cancers and the second leading cause of cancer-related deaths in men in the United States. A large number of patients undergo radiation therapy (RT) as a standard care of treatment; however, RT causes erectile dysfunction (radiation-induced erectile dysfunction; RiED) because of late side effects after RT that significantly affects quality of life of prostate cancer patients. Within 5 years of RT, approximately 50% of patients could develop RiED. Based on the past and current research findings and number of publications from our group, the precise mechanism of RiED is under exploration in detail. Recent investigations have shown prostate RT induces significant morphologic arterial damage with aberrant alterations in internal pudendal arterial tone. Prostatic RT also reduces motor function in the cavernous nerve which may attribute to axonal degeneration may contributing to RiED. Furthermore, the advances in radiogenomics such as radiation induced somatic mutation identification, copy number variation and genome-wide association studies has significantly facilitated identification of biomarkers that could be used to monitoring radiation-induced late toxicity and damage to the nerves; thus, genomic- and proteomic-based biomarkers could greatly improve treatment and minimize arterial tissue and nerve damage. Further, advanced technologies such as proton beam therapy that precisely target tumor and significantly reduce off-target damage to vital organs and healthy tissues. In this review, we summarize recent advances in RiED research and novel treatment modalities for RiED. We also discuss the possible molecular mechanism involved in the development of RiED in prostate cancer patients. Further, we discuss various readily available methods as well as novel strategies such as stem cell therapies, shockwave therapy, nerve grafting with tissue engineering, and nutritional supplementations might be used to mitigate or cure sexual dysfunction following radiation treatment.

The development, commercialization, and clinical context of yttrium-90 radiolabeled resin and glass microspheres.

Abstract: Selective internal radiation therapy has emerged as a well-accepted therapeutic for primary and metastatic hepatic malignancies. This therapeutic modality requires the combined efforts of multiple medical disciplines to ensure the safe delivery of yttrium-90 (90Y)-labeled microspheres. The development of this therapy followed decades of clinical research involving tumor vascularity and microsphere development. Today, it is essential that treating physicians have a thorough understanding of hepatic tumor vascularity and 90Y microsphere characteristics before undertaking this complex intervention. This review explores the contributions of early investigators of this therapy, as well as the development, US Food and Drug Administration approval, manufacturing process, and attributes of the 2 commercially available 90Y radiolabeled microsphere device to clarify the key physical differences between the products.

The big data effort in radiation oncology: Data mining or data farming?

Abstract: Although large volumes of information are entered into our electronic health care records, radiation oncology information systems and treatment planning systems on a daily basis, the goal of extracting and using this big data has been slow to emerge. Development of strategies to meet this goal is aided by examining issues with a data farming instead of a data mining conceptualization. Using this model, a vision of key data elements, clinical process changes, technology issues and solutions, and role for professional societies is presented. With a better view of technology, process and standardization factors, definition and prioritization of efforts can be more effectively directed.

Stereotactic body radiotherapy (SBRT) for locally advanced extrahepatic and intrahepatic cholangiocarcinoma

Abstract: Objectives We report single-institution clinical efficacy and safety outcomes for patients with unresectable locally advanced cholangiocarcinoma who were treated with stereotactic body radiation therapy (SBRT) and a subset of patients who received neoadjuvant SBRT and chemotherapy as part of an orthotopic liver transplantation (OLT) protocol Methods and materials From October 2008 to June 2015, 31 consecutive patients with unresectable extrahepatic (n = 25) or intrahepatic (n = 6) cholangiocarcinoma were treated with SBRT and retrospectively analyzed Four patients underwent liver transplantation, and 1 underwent resection SBRT was delivered in 5 fractions with a median dose of 40 Gy Toxicity was scored using the Common Terminology Criteria for Adverse Events Version 40 Overall survival (OS), time to progression, and local control were estimated using the Kaplan-Meier method Results The median follow-up time was 115 months The 1- and 2-year OS rates were 59% and 33%, respectively, with a median survival of 157 months The 1- and 2-year freedom from progression was 67% and 34%, respectively Median time to progression was 168 months Nine patients had local failure The actuarial 1- and 2-year local control rates were 78% and 47%, respectively Among patients who also had OLT, the median OS was 313 months Twenty-four patients (77%) experienced some form of acute grade 1-2 toxicity, most commonly fatigue or pain Five patients (16%) experienced grade ≥3 toxicity Conclusions SBRT is a promising option for patients with unresectable or recurrent cholangiocarcinoma either as a component of neoadjuvant therapy prior to OLT or as part of definitive therapy for patients who are unresectable and not eligible for transplantation

Viability of Noncoplanar VMAT for liver SBRT compared with coplanar VMAT and beam orientation optimized 4π IMRT

Abstract: Purpose The 4π static noncoplanar radiation therapy delivery technique has demonstrated better normal tissue sparing and dose conformity than the clinically used volumetric modulated arc therapy (VMAT). It is unclear whether this is a fundamental limitation of VMAT delivery or the coplanar nature of its typical clinical plans. The dosimetry and the limits of normal tissue toxicity constrained dose escalation of coplanar VMAT, noncoplanar VMAT and 4π radiation therapy are quantified in this study. Methods and materials Clinical stereotactic body radiation therapy plans for 20 liver patients receiving 30 to 60 Gy using coplanar VMAT (cVMAT) were replanned using 3 to 4 partial noncoplanar arcs (nVMAT) and 4π with 20 intensity modulated noncoplanar fields. The conformity number, homogeneity index, 50% dose spillage volume, normal liver volume receiving >15 Gy, dose to organs at risk (OARs), and tumor control probability were compared for all 3 treatment plans. The maximum tolerable dose yielding a normal liver normal tissue control probability Results Compared with cVMAT, the nVMAT and 4π plans reduced liver volume receiving >15 Gy by an average of 5 cm3 and 80 cm3, respectively. 4π reduced the 50% dose spillage volume by ∼23% compared with both VMAT plans, and either significantly decreased or maintained OAR doses. The 4π maximum tolerable doses and survival fractions were significantly higher than both cVMAT and nVMAT (P Conclusions The 4π technique provides significantly better OAR sparing than both cVMAT and nVMAT and enables more clinically relevant dose escalation for tumor local control. Therefore, despite the current accessibility of nVMAT, it is not a viable alternative to 4π for liver SBRT.

Use of mobile device technology to continuously collect patient-reported symptoms during radiation therapy for head and neck cancer: A prospective feasibility study.

Abstract: Purpose Accurate assessment of toxicity allows for timely delivery of supportive measures during radiation therapy for head and neck cancer. The current paradigm requires weekly evaluation of patients by a provider. The purpose of this study is to evaluate the feasibility of monitoring patient reported symptoms via mobile devices. Methods and materials We developed a mobile application for patients to report symptoms in 5 domains using validated questions. Patients were asked to report symptoms using a mobile device once daily during treatment or more often as needed. Clinicians reviewed patient-reported symptoms during weekly symptom management visits and patients completed surveys regarding perceptions of the utility of the mobile application. The primary outcome measure was patient compliance with mobile device reporting. Compliance is defined as number of days with a symptom report divided by number of days on study. Results There were 921 symptom reports collected from 22 patients during treatment. Median reporting compliance was 71% (interquartile range, 45%-80%). Median number of reports submitted per patient was 34 (interquartile range, 21-53). Median number of reports submitted by patients per week was similar throughout radiation therapy and there was significant reporting during nonclinic hours. Patients reported high satisfaction with the use of mobile devices to report symptoms. Conclusions A substantial percentage of patients used mobile devices to continuously report symptoms throughout a course of radiation therapy for head and neck cancer. Future studies should evaluate the impact of mobile device symptom reporting on improving patient outcomes.

A prospective study of quality of life in breast cancer patients undergoing radiation therapy

Abstract: Purpose The purpose of this study was to examine the impact of radiation therapy on quality of life (QOL) of breast cancer patients during and until 1 year after radiation therapy treatment. Methods and materials Thirty-nine breast cancer patients treated with breast-conserving surgery were enrolled in a prospective study before whole breast radiation therapy (50 Gy plus a 10-Gy boost). No patient received chemotherapy. Data were collected before, at week 6 of radiation therapy, and 6 weeks and 1 year after radiation therapy. The primary outcome variable was quality of life (QOL), measured by Medical Outcomes Study 36-Item Short Form Version 2 (SF-36). Risk factors potentially associated with total SF-36 scores and its physical and mental health component summary scores were also examined, including age, race, marital status, smoking history, menopausal status, endocrine treatment, cancer stage, sleep abnormalities (assessed by the Pittsburgh Sleep Quality Index), and perceived stress levels (assessed by the Perceived Stress Scale). Mixed effect modeling was used to observe QOL changes during and after radiation therapy. Results Total SF-36 scores did not change significantly during and up to 1 year after radiation therapy compared with baseline measures. Nevertheless, increased body mass index (BMI) and increased perceived stress were predictive of reduced total SF-36 scores over time (P = .0064, and P Conclusions Radiation therapy did not worsen QOL in breast cancer patients. However, pre-radiation therapy patient characteristics including BMI and perceived stress may be used to identify women who may experience decreased physical and mental function during and up to 1 year after radiation therapy.

Postoperative radiation therapy is associated with a reduced risk of local recurrence among low risk Merkel cell carcinomas of the head and neck.

Abstract: Purpose Merkel cell carcinoma (MCC) is a rare and often aggressive skin cancer. Typically, surgery is the primary treatment. Postoperative radiation therapy (PORT) is often recommended to improve local control. It is unclear whether PORT is indicated in patients with favorable Stage IA head and neck (HN) MCC. Methods and materials We conducted a retrospective analysis of 46 low-risk HN MCC cases treated between 2006 and 2015. Inclusion criteria were defined as a primary tumor size of ≤ 2 cm, negative pathological margins, negative sentinel lymph node biopsy, and no immunosuppression. Local recurrence (LR) was defined as tumor recurrence within 2 cm of the primary surgical bed and estimated with the Kaplan-Meier method. Results Omission of PORT was offered to all 46 patients, of which 23 patients received PORT and 23 did not. No patient received adjuvant chemotherapy. There were no significant differences in surgical margins, tumor size, depth, lympho-vascular invasion status, or demographics between the two patient groups. Median follow-up for all patients was 3.7 years. Six of the 23 patients who did not receive PORT developed an LR. Compared to the group that received PORT, there was a significantly higher risk of LR in the group treated without PORT (26% vs. 0%, P = .02). Median time to LR was 11 months. All local failures were effectively salvaged. There was no difference in MCC-specific and overall survival between the 2 groups. Conclusions For patients with HN MCC, omission of PORT was associated with a significantly higher risk of local recurrence even among those patients with the lowest-risk tumors (i.e., Stage IA without immune suppression). Thus, it is important to weigh the benefits of PORT against the side effect profile on a case-specific basis for each patient.

Modeling of chronic radiation-induced cystitis in mice.

Abstract: Purpose Radiation cystitis (RC), a severe inflammatory bladder condition, develops as a side effect of pelvic radiation therapy in cancer patients. There are currently no effective therapies to treat RC, in part from the lack of preclinical model systems. In this study, we developed a mouse model for RC and used a Small Animal Radiation Research Platform to simulate the targeted delivery of radiation as used with human patients. Methods and materials To induce RC, C3H mice received a single radiation dose of 20 Gy delivered through 2 beams. Mice were subjected to weekly micturition measurements to assess changes in urinary frequency. At the end of the study, bladder tissues were processed for histology. Results Radiation was well-tolerated; no change in weight was observed in the weeks after treatment, and there was no hair loss at the irradiation sites. Starting at 17 weeks after treatment, micturition frequency was significantly higher in irradiated mice versus control animals. Pathological changes include fibrosis, inflammation, urothelial thinning, and necrosis. At a site of severe insult, we observed telangiectasia, absence of uroplakin-3 and E-cadherin relocalization. Conclusions We developed an RC model that mimics the human pathology and functional changes. Furthermore, radiation exposure attenuates the urothelial integrity long-term, allowing for potential continuous irritability of the bladder wall from exposure to urine. Future studies will focus on the underlying molecular changes associated with this condition and investigate novel treatment strategies.

Oncoplastic breast surgery in the setting of breast-conserving therapy: A systematic review

Abstract: Breast-conserving therapy (BCT), or breast-conserving surgery with adjuvant radiation therapy, has become a standard treatment alternative to mastectomy for women with early-stage breast cancer after many long-term studies have reported comparable rates of overall survival and local control. Oncoplastic breast surgery in the setting of BCT consists of various techniques that allow for an excision with a wider margin and a simultaneous enhancement of cosmetic sequelae, making it an ideal breast cancer surgery. Because of the parenchymal rearrangement that is routinely involved in oncoplastic techniques, however, the targeted tissue can be relocated, thus posing a challenge to localize the tumor bed for radiation planning. The goals of this systematic review are to address the challenges, outcomes, and cosmesis of oncoplastic breast surgery in the setting of BCT.

An analysis of prognostic factors associated with recurrence in the treatment of atypical meningiomas

Abstract: Background There has been increased reporting of atypical meningioma (grade II) since the World Health Organization reclassification in 2000, and the use of postoperative radiation therapy (RT) in the treatment of these tumors is controversial. We evaluated patients treated at our institution to identify patient subgroups with increased risk of recurrence that may benefit from adjuvant RT. Methods and materials We retrospectively assessed 50 patients treated for World Health Organization grade II meningiomas between March 2000 and February 2013. Sex, race, age of diagnosis, tumor location, performance status, size of tumor, MIB-1 index, resection status, and RT were recorded. Patient follow-up, recurrence, and vital status were measured to assess 3-year overall survival (OS) and recurrence free survival (RFS). Results The median follow-up was 37 months (range, 1-148). Female sex was associated with decreased RFS compared with male sex (86.1% vs 100%, P = .047). Subtotal resection demonstrated both inferior RFS (67.5% vs 96.6%, P = .025) and OS compared with gross total resection (70.0% vs 100%, P 4.5 cm had worse RFS than tumors ≤4.5 cm (85.4% vs 100%, P = .025). Patient OS was lower in tumors with an MIB-1 index >5% than ≤5% (89.7% vs 100%, P = .008). Eastern Cooperative Oncology Group 2-4 negatively impacted OS relative to patients with an Eastern Cooperative Oncology Group 0-1 (66.7% vs 100%, P Conclusions Significantly higher rates of recurrence occurred in female sex, subtotal resection, and tumors larger than 4.5 cm. Further studies are needed to confirm these findings and determine whether patients without any of these risk factors can undergo surgical resection without adjuvant radiation therapy.

Use of acupuncture to alleviate side effects in radiation oncology: Current evidence and future directions.

Abstract: Several reports have shown that acupuncture is an effective method of complementary medicine; however, only a few of these reports have focused on oncological patients treated with radiation therapy. Most of these studies discuss a benefit of acupuncture for side-effect reduction; however, not all could demonstrate significant improvements. Thus, innovative trial designs are necessary to confirm that acupuncture can alleviate side effects related to radiation therapy. In the present manuscript, we perform a broad review and discuss pitfalls and limitations of acupuncture in parallel with standard radiation therapy, which lead the way to novel treatment concepts.

Efficacy and toxicity of rectal cancer reirradiation using IMRT for patients who have received prior pelvic radiation therapy.

Abstract: Purpose Locally recurrent rectal cancer may cause significant morbidity. Prior reports of rectal cancer reirradiation following local recurrence suggest treatment efficacy, with variable rates of late toxicity. Modern techniques including intensity modulated radiation therapy (IMRT) may improve the therapeutic index. We report outcomes for pelvic reirradiation as treatment for rectal cancer using IMRT. Methods and materials The records of 31 patients undergoing reirradiation for rectal cancer between 2004 and 2013 were reviewed. All patients underwent IMRT using an accelerated hyperfractionation (39 Gy in 1.5-Gy fractions delivered twice daily, n=15) or once-daily fractionation technique (median dose, 30.4 Gy; range, 27-40 Gy in 15-22 fractions; n = 16). The median cumulative dose was 77 Gy (range, 59-113), and the median interval from prior pelvic radiation therapy was 39.8 months (range, 10.1-307.6). Treatment intent was palliative in 20 patients and neoadjuvant or adjuvant in 11 patients. Surgery was generally reserved for patients with an isolated local recurrence. Concurrent chemotherapy was administered for 25/31 patients, most frequently capecitabine (n=11) or continuous infusion 5-fluorouracil (n=10). Results Median follow-up was 11.3 months. The prescribed treatment was completed in 29/31 patients (93.5%). Among 18 patients with symptoms attributable to recurrent disease, successful palliation was achieved in 10/18 (55.6%). The rate of grade 2 and grade 3 acute toxicities was 32.3% and 3.2%, respectively. Local control rates at 1 and 2 years were 61.3% and 47.3%, respectively. Median overall survival was 21.9 months, and 1-year survival was 66.7% for patients who had surgical resection versus 58.7% for those who did not ( P = .0802). Conclusions Rectal cancer reirradiation using IMRT is well-tolerated in the setting of prior pelvic radiation therapy. Given significant risk of local progression, further dose escalation may be warranted for patients with life expectancy exceeding 1 year.

Detection of late radiation damage on left atrial fibrosis using cardiac late gadolinium enhancement magnetic resonance imaging

Abstract: Purpose This is a proof-of-principle study investigating the feasibility of using late gadolinium enhancement magnetic resonance imaging (LGE-MRI) to detect left atrium (LA) radiation damage. Methods and materials LGE-MRI data were acquired for 7 patients with previous external beam radiation therapy (EBRT) histories. The enhancement in LA scar was delineated and fused to the computed tomography images used in dose calculation for radiation therapy. Dosimetric and normal tissue complication probability analyses were performed to investigate the relationship between LA scar enhancement and radiation doses. Results The average LA scar volume for the subjects was 2.5 cm3 (range, 1.2-4.1 cm3; median, 2.6 cm3). The overall average of the mean dose to the LA scar was 25.9 Gy (range, 5.8-49.2 Gy). Linear relationships were found between the amount of radiation dose (mean dose) (R2 = 0.8514, P = .03) to the LA scar-enhanced volume. The ratio of the cardiac tissue change (LA scar/LA wall) also demonstrated a linear relationship with the level of radiation received by the cardiac tissue (R2 = 0.9787, P < .01). Last, the normal tissue complication probability analysis suggested a dose response function to the LA scar enhancement. Conclusions With LGE-MRI and 3-dimensional dose mapping on the treatment planning system, it is possible to define subclinical cardiac damage and distinguish intrinsic cardiac tissue change from radiation induced cardiac tissue damage. Imaging myocardial injury secondary to EBRT using MRI may be a useful modality to follow cardiac toxicity from EBRT and help identify individuals who are more susceptible to EBRT damage. LGE-MRI may provide essential information to identify early screening strategy for affected cancer survivors after EBRT treatment.

Disparities in staging prostate magnetic resonance imaging utilization for nonmetastatic prostate cancer patients undergoing definitive radiation therapy.

Abstract: Purpose There is growing evidence supporting incorporating multiparametric (mp) magnetic resonance imaging (MRI) scans into risk stratification, active surveillance, and treatment paradigms for prostate cancer. The purpose of our study was to determine whether demographic disparities exist in staging MRI utilization for prostate cancer patients. Methods and materials An institutional database of 705 nonmetastatic prostate cancer patients treated with radiation therapy from 2005 through 2013 was used to identify patients undergoing versus not undergoing pretreatment diagnostic prostate mpMRI. Uni- and multivariable logistic regression evaluated the relationship of clinical and demographic characteristics with MRI utilization. Results All demographic variables assessed, except the other race category, were significantly associated with MRI utilization (all P < .05), including age (odds ratio [OR], 0.92), black race (OR, 0.51), poverty (OR, 0.53), closer distance to radiation facility (OR, 1.79), and nonprivate primary insurance (OR, 0.57) on univariable analysis, while clinical stage T3 (OR, 3.37) was the only clinical characteristic. On multivariable analysis stratified by D'Amico risk group, age remained significant across all risk groups, whereas the black versus white racial (OR, 0.21; 95% confidence interval, 0.08-0.55) and nonprivate versus private insurance type (OR, 0.37; 95% confidence interval, 0.16-0.86) disparities persisted in the low-risk group. Clinical stage T3 remained associated in the high-risk group. For race specifically, the percentages of whites, blacks, and others undergoing MRI in the overall cohort and by risk group were, respectively: overall, 80% (343/427), 68% (156/231), and 85% (40/47); low risk, 86%, 56%, and 63%; intermediate risk, 79%, 72%, and 95%; and high risk, 72%, 72%, and 100%. Conclusions In this urban, academic center cohort, older patients across all risk groups and black or nonprivate insurance patients in the low risk group were less likely to undergo staging prostate MRI scans. Further research should investigate these differences to ensure equitable utilization across all demographic groups considering the burden of prostate cancer disparities.

Intracoronary brachytherapy for in-stent restenosis of drug-eluting stents.

Abstract: Purpose: Given the limited salvage options for in-stent restenosis (ISR) of drug-eluting stents (DES), our high-volume cardiac catheterization laboratory has been performing intracoronary brachytherapy (ICBT) in patients with recurrent ISR of DES. This study analyzes their baseline characteristics and assesses the safety/toxicity of ICBT in this high-risk population. Methods and materials: A retrospective analysis of patients treated with ICBT between September 2012 and December 2014 was performed. Patients with ISR twice in a single location were eligible. Procedural complications included vessel dissection, perforation, tamponade, slow/absent blood flow, and vessel closure. Postprocedural events included myocardial infarction, coronary artery bypass graft, congestive heart failure, stroke, bleeding, thrombosis, embolism, dissection, dialysis, or death occurring within 72 hours. A control group of patients with 2 episodes of ISR at 1 location who underwent percutaneous coronary intervention without ICBT was identified. Unpaired t tests and c 2 tests were used to compare the groups. Results: There were 134 (78%) patients in the ICBT group with 141 treated lesions and 37 (22%) patients in the control group. There was a high prevalence of hyperlipidemia (>95%), hypertension (>95%), and diabetes (>50%) in both groups. The groups were well-balanced with respect to age, sex, and pre-existing medical conditions, with the exception of previous coronary artery bypass graft being more common the ICBT group. Procedural complication rates were low in the control and ICBT groups (0% vs 4.5%, P Z .190). Postprocedural event rates were low (<5%) in both groups. Readmission rate at 30 days was 3.7% in the ICBT group and 5.4% in the control group (P Z .649). Conclusions: This is the largest recent known series looking at ICBT for recurrent ISR of DES. ICBT is a safe treatment option with similarly low rates (<5%) of procedural and postprocedural complications compared with percutaneous coronary intervention alone. This study establishes the safety of ICBT in a high-risk patient cohort.

Management approach for recurrent brain metastases following upfront radiosurgery may affect risk of subsequent radiation necrosis

Abstract: Purpose Many patients treated with stereotactic radiosurgery (SRS) alone as initial treatment require 1 or more subsequent salvage therapies. This study aimed to determine if commonly used salvage strategies are associated with differing risks of radiation necrosis (RN). Methods and materials All patients treated with upfront SRS alone for brain metastases at our institution were retrospectively analyzed. Salvage treatment details were obtained for brain failures. Patients who underwent repeat SRS to the same lesion were excluded. RN was determined based on pathological confirmation or advanced brain imaging consistent with RN in a symptomatic patient. Patients were grouped according to salvage treatment and rates of RN were compared via Fisher's exact tests. Results Of 284 patients treated with upfront SRS alone, 132 received salvage therapy and 44 received multiple salvage treatments. This included 31 repeat SRS alone, 58 whole brain radiation therapy (WBRT) alone, 28 SRS and WBRT, 7 surgery alone, and 8 surgery with adjuvant radiation. With a median follow-up of 10 months, the rate of RN among all patients was 3.17% (9/284), salvaged patients 4.55% (6/132), and never salvaged patients 1.97% (3/152). Receiving salvage therapy did not significantly increase RN risk (P = .31). Of the patients requiring salvage treatments, the highest RN rate was among patients that had both salvage SRS and WBRT (delivered as separate salvage therapies) (6/28, 21.42%). RN rate in this group was significantly higher than in those treated with repeat SRS alone (0/31), WBRT alone (0/58), surgery alone (0/7), and surgery with adjuvant radiation (0/8). Comparing salvage WBRT doses <30 Gy versus ≥30 Gy revealed no effect of dose on RN rate. Additionally, among patients who received multiple SRS treatments, number of treated lesions was not predictive of RN incidence. Conclusion Our results suggest that initial management approach for recurrent brain metastasis after upfront SRS does not affect the rate of RN. However, the risk of RN significantly increases when patients are treated with both repeat SRS and salvage WBRT. Methods to improve prediction of toxicity and optimize patient selection for salvage treatments are needed.

Manufacture and evaluation of 3-dimensional printed sizing tools for use during intraoperative breast brachytherapy

Abstract: Three-dimensional (3D) printing has emerged as a promising modality for the production of medical devices. Here we describe the design, production, and implementation of a series of sizing tools for use in an intraoperative breast brachytherapy program. These devices were produced using a commercially available low-cost 3D printer and software, and their implementation resulted in an immediate decrease in consumable costs without affecting the quality of care or the speed of delivery. This work illustrates the potential of 3D printing to revolutionize the field of medical devices, enabling physicians to rapidly develop and prototype novel tools.

Feasibility of automated 3-dimensional magnetic resonance imaging pancreas segmentation

Abstract: Purpose With the advent of magnetic resonance imaging (MRI) guided radiation therapy, internal organ motion can be imaged simultaneously during treatment. In this study, we evaluate the feasibility of pancreas MRI segmentation using state-of-the-art segmentation methods. Methods and materials T2-weighted half-Fourier acquisition single-shot turbo spin-echo and T1 weighted volumetric interpolated breath-hold examination images were acquired on 3 patients and 2 healthy volunteers for a total of 12 imaging volumes. A novel dictionary learning (DL) method was used to segment the pancreas and compared to t mean-shift merging, distance regularized level set, and graph cuts, and the segmentation results were compared with manual contours using Dice's index, Hausdorff distance, and shift of the center of the organ (SHIFT). Results All volumetric interpolated breath-hold examination images were successfully segmented by at least 1 of the autosegmentation method with Dice's index >0.83 and SHIFT ≤2 mm using the best automated segmentation method. The automated segmentation error of half-Fourier acquisition single-shot turbo spin-echo images was significantly greater. DL is statistically superior to the other methods in Dice’s overlapping index. For the Hausdorff distance and SHIFT measurement, distance regularized level set and DL performed slightly superior to the graph cuts method, and substantially superior to mean-shift merging. DL required least human supervision and was faster to compute. Conclusions Our study demonstrated potential feasibility of automated segmentation of the pancreas on MRI scans with minimal human supervision at the beginning of imaging acquisition. The achieved accuracy is promising for organ localization.

Feasibility of 4D perfusion CT imaging for the assessment of liver treatment response following SBRT and sorafenib.

Abstract: Objectives To evaluate the feasibility of 4-dimensional perfusion computed tomography (CT) as an imaging biomarker for patients with hepatocellular carcinoma and metastatic liver disease. Methods and materials Patients underwent volumetric dynamic contrast-enhanced CT on a 320-slice scanner before and during stereotactic body radiation therapy and sorafenib, and at 1 and 3 months after treatment. Quiet free breathing was used in the CT acquisition and multiple techniques (rigid or deformable registration as well as outlier removal) were applied to account for residual liver motion. Kinetic modeling was performed on a voxel-by-voxel basis in the gross tumor volume and normal liver resulting in 3-dimensional parameter maps of blood perfusion, capillary permeability, blood volume, and mean transit time. Perfusion characteristics in the tumor and adjacent liver were correlated with radiation dose distributions to evaluate dose-response. Paired t tests assessed change in spatial and histogram parameters from baseline to different time points during and after treatment. Technique reproducibility as well as the impact of arterial and portal vein input functions was also investigated using intra- and inter-subject variance and Bland-Altman analysis. Results Quantitative perfusion parameters were reproducible (±5.7%; range, 2%-10%) depending on tumor/normal liver type and kinetic parameter. Statistically significant reductions in tumor perfusion were measurable over the course of treatment and as early as 1 week after sorafenib administration ( P 2 = 0.95) that increased significantly over the course treatment. Conclusions The proposed methodology demonstrated feasibility of evaluating spatiotemporal changes in liver tumor perfusion and normal liver function following antiangiogenic therapy and radiation treatment warranting further evaluation of biomarker prognostication.

Severe radiation-induced leukoencephalopathy: Case report and literature review.

Abstract: a Department of Radiation Oncology, James P. Wilmot Cancer Institute, University of Rochester, Rochester, New York b Division of Hematology/Oncology, James P. Wilmot Cancer Institute, University of Rochester, Rochester, New York c Department of Neurology, James P. Wilmot Cancer Institute, University of Rochester, Rochester, New York d Department of Neurosurgery, James P. Wilmot Cancer Institute, University of Rochester, Rochester, New York

Functional imaging equivalence and proof of concept for image-guided adaptive radiotherapy with fixed gantry and rotating couch.

Abstract: Purpose The purpose of this article is to present the first imaging experiments to demonstrate the functional equivalence between a conventional rotational gantry and a fixed-beam imaging geometry, and the feasibility of an iterative image-reconstruction technique under gravitational deformation. Methods and materials Experiments were performed using an Elekta Axesse with Agility MLC and XVI, a custom-built rotating phantom stage, a Catphan QA phantom, and a porcine heart. For the imaging equivalence, a conventional cone beam computed tomography (CBCT) of the Catphan was acquired, as well as a set of 660 x-ray projections with a static gantry and rotating Catphan. Both datasets were reconstructed with the Feldkamp-Davis-Kress (FDK) algorithm, and the resultant volumetric images were compared using standard metrics. For imaging under gravitational deformation, a conventional CBCT of the Catphan and a set of 660 x-ray projections with a static gantry and rotating Catphan were also acquired with a porcine heart. The conventional CBCT was reconstructed using FDK. The projections that were acquired with the heart rotating were sorted into angular bins and reconstructed with prior image constrained compressed sensing using a deformation-blurred FDK prior. Deformation was quantified with B-spline transformation-based deformable image registration. Results For imaging equivalence, the difference between the two Catphan images was consistent with Poisson noise. For imaging under gravitational deformation, the conventional CBCT porcine heart image (ground truth at 0 degrees) matched the static gantry, rotating heart reconstruction with a mean magnitude of Conclusions We have demonstrated imaging equivalence in cone beam CT reconstructions between rigid phantom images acquired with a conventional rotating gantry and with a fixed-gantry and rotating phantom. We have presented a method for image reconstruction under a fixed-beam imaging geometry using a deformable phantom.

Preplanning prediction of the left anterior descending artery maximum dose based on patient, dosimetric, and treatment planning parameters

Abstract: Purpose Maximum dose to the left anterior descending artery (LADmax) is an important physical constraint to reduce the risk of cardiovascular toxicity. We generated a simple algorithm to guide the positioning of the tangent fields to reliably maintain LADmax Methods and materials Dosimetric plans from 146 consecutive women treated prone to the left breast enrolled in prospective protocols of accelerated whole breast radiation therapy, with a concomitant daily boost to the tumor bed (40.5 Gy/15 fraction to the whole breast and 48 Gy to the tumor bed), provided the training set for algorithm development. Scatter plots and correlation coefficients were used to describe the bivariate relationships between LADmax and several parameters: distance from the tumor cavity to the tangent field edge, cavity size, breast separation, field size, and distance from the tangent field. A logistic sigmoid curve was used to model the relationship of LADmax and the distance from the tangent field. Furthermore, we tested this prediction model on a validation data set of 53 consecutive similar patients. Results A lack of linear relationships between LADmax and distance from cavity to LAD (−0.47), cavity size (−0.18), breast separation (−0.02), or field size (−0.28) was observed. In contrast, distance from the tangent field was highly negatively correlated to LADmax (-0.84) and was used in the models to predict LADmax. From a logistic sigmoid model we selected a cut-point of 2.46 mm (95% confidence interval, 2.19-2.74 mm) greater than which LADmax is Conclusions Placing the edge of the tangents at least 2.5 mm from the closest point of the contoured LAD is likely to assure LADmax is

Chemoradiation therapy with docetaxel in elderly patients with stage II/III esophageal cancer: A phase 2 trial

Abstract: Purpose The most effective treatments in elderly patients with esophageal cancer remain a subject of debate. This multicenter phase 2 study was designed to evaluate the efficacy and toxicity of chemoradiation therapy (CRT) with docetaxel (DTX) in elderly patients with stage II/III (non-T4) esophageal cancer. Methods and materials Patients ≥70 years of age with clinical stage II/III esophageal cancer received DTX at a weekly dose of 10 mg/m2 during 6 consecutive weeks and concurrent radiation therapy (60 Gy in 30 fractions). The primary endpoint was the 2-year survival rate, and the required number of enrolled patients was 37. Results Between July 2008 and January 2011, 16 patients were enrolled. The study was prematurely closed because of slow accrual. Characteristics of the patients were as follows: median age, 77 years (range, 73-81); performance status 0/1, 4/12; and clinical stage IIA/IIB/III, 3/4/9. Of the 16 patients, 14 (87.5%) completed the CRT. The 2-year survival rate was 62.5% (90% confidence interval [CI], 42.5-82.5). The median survival time was 27.7 months (95% CI, 23.3-32.2 months) and the median progression-free survival was 15.2 months (95% CI, 5.4-25.0 months). Seven patients achieved complete response, resulting in a complete response rate of 43.8% (95% CI, 19.8-70.1). Grade 3 or higher acute toxicities included esophagitis (31.3%), anorexia (12.5%), leukopenia (6.3%), neutropenia (6.3%), thrombocytopenia (6.3%), mucositis (6.3%), and infection (6.3%). Grade 3 or higher late toxicities included esophagitis (12.5%), pleural effusion (12.5%), pneumonitis (6.3%), and pericardial effusion (6.3%). Conclusions CRT with DTX might be a treatment option for elderly patients with stage II/III esophageal cancer, particularly for patients who are medically unfit for surgery or cisplatin-containing therapy. However, further improvements of this therapy are required to decrease the incidence of esophagitis.

Myeloablative conditioning with total body irradiation for AML: Balancing survival and pulmonary toxicity

Abstract: Purpose The purpose of this study was to compare leukemia-free survival (LFS) and other clinical outcomes in patients with acute myelogenous leukemia who underwent a myeloablative allogeneic stem cell transplant with and without total body irradiation (TBI). Methods and materials Adult patients with acute myelogenous leukemia undergoing myeloablative allogeneic stem cell transplant at Duke University Medical Center between 1995 and 2012 were included. The primary endpoint was LFS. Secondary outcomes included overall survival (OS), nonrelapse mortality, and the risk of pulmonary toxicity. Kaplan-Meier survival estimates and Cox proportional hazards multivariate analyses were performed. Results A total of 206 patients were evaluated: 90 received TBI-based conditioning regimens and 116 received chemotherapy alone. Median follow-up was 36 months. For all patients, 2-year LFS and OS were 36% (95% confidence interval [CI], 29-43) and 39% (95% CI, 32-46), respectively. After adjusting for known prognostic factors using a multivariate analysis, TBI was associated with improved LFS (hazard ratio: 0.63; 95% CI: 0.44-0.91) and OS (hazard ratio: 0.63; 95% CI, 0.43-0.91). There was no difference in nonrelapse mortality between cohorts, but pulmonary toxicity was significantly more common with TBI (2-year incidence 42% vs 12%, P Conclusions TBI-based regimens were associated with superior LFS and OS but at the cost of increased pulmonary toxicity.

Priority-driven plan optimization in locally advanced lung patients based on perfusion SPECT imaging

Abstract: Purpose Limits on mean lung dose (MLD) allow for individualization of radiation doses at safe levels for patients with lung tumors However, MLD does not account for individual differences in the extent or spatial distribution of pulmonary dysfunction among patients, which leads to toxicity variability at the same MLD We investigated dose rearrangement to minimize the radiation dose to the functional lung as assessed by perfusion single photon emission computed tomography (SPECT) and maximize the target coverage to maintain conventional normal tissue limits Methods and materials Retrospective plans were optimized for 15 patients with locally advanced non-small cell lung cancer who were enrolled in a prospective imaging trial A staged, priority-based optimization system was used The baseline priorities were to meet physical MLD and other dose constraints for organs at risk, and to maximize the target generalized equivalent uniform dose (gEUD) To determine the benefit of dose rearrangement with perfusion SPECT, plans were reoptimized to minimize the generalized equivalent uniform functional dose (gEUfD) to the lung as the subsequent priority Results When only physical MLD is minimized, lung gEUfD was 126 ± 49 Gy (63-217 Gy) When the dose is rearranged to minimize gEUfD directly in the optimization objective function, 10 of 15 cases showed a decrease in lung gEUfD of >20% (lung gEUfD mean 99 ± 43 Gy, range 21-162 Gy) while maintaining equivalent planning target volume coverage Although all dose-limiting constraints remained unviolated, the dose rearrangement resulted in slight gEUD increases to the cord (54 ± 39 Gy), esophagus (30 ± 37 Gy), and heart (23 ± 26 Gy) Conclusions Priority-driven optimization in conjunction with perfusion SPECT permits image guided spatial dose redistribution within the lung and allows for a reduced dose to the functional lung without compromising target coverage or exceeding conventional limits for organs at risk

Feasibility and safety of cavity-directed stereotactic radiosurgery for brain metastases at a high-volume medical center

Abstract: Objective Our objective was to report safety and efficacy of stereotactic radiosurgery (SRS) to the surgical bed following resection of brain metastases. Methods Eighty-seven consecutive patients who underwent cavity-directed SRS to the operative bed for the treatment of brain metastases between 2002 and 2010 were evaluated. SRS required a gadolinium-enhanced, high-resolution, T1-weighted magnetic resonance imaging for tumor targeting and delivered a median dose of 18 Gy (14-22 Gy) prescribed to encompass the entire resection cavity. Whole brain irradiation was reserved for salvage. Patients were followed every 3 months with clinical examination and magnetic resonance imaging. Overall survival, local and regional recurrence, and factors affecting these outcomes were evaluated using Kaplan-Meier and log-rank analyses. Results The median imaging follow-up was 7.1 months, with >40% of patients having imaging for ≥1 year. Local control at 1 and 2 years was 82% and 75%, respectively. Cavity recurrence was more common with a tumor diameter >3 cm (P 14 mL (P 3 cm were 100%, 86%, and 72%, respectively. Neither subtotal resection nor target margins >2 mm to 3 mm affected local control. The median overall survival was 14.3 months with actuarial 5-year survival of 20%. Actuarial regional central nervous system recurrence was 44% at 1 year. On univariate analysis, only the presence of extracranial disease was associated with survival (P Conclusions Excellent local control is achievable with cavity-directed SRS in well-selected patients, particularly for lesions with diameter

Intravenous contrast-enhanced cone beam computed tomography (IVCBCT) of intrahepatic tumors and vessels

Abstract: Purpose Liver tumors are challenging to visualize on cone beam computed tomography (CBCT) without intravenous (IV) contrast. Image guidance for liver cancer stereotactic body ablative radiation therapy (SABR) could be improved with the direct visualization of hepatic tumors and vasculature. This study investigated the feasibility of the use of IV contrast-enhanced CBCT (IV-CBCT) as a means to improve liver target visualization. Methods and Materials Patients on a liver SABR protocol underwent IV-CBCT before 1 or more treatment fractions in addition to a noncontrast CBCT. Image acquisition was initiated 0 to 30 seconds following injection and acquired over 60 to 120 seconds. “Stop and go” exhale breath-hold CBCT scans were used whenever feasible. Changes in mean CT number in regions of interest within visible vasculature, tumor, and adjacent liver were quantified between CBCT and IV-CBCT. Results Twelve pairs of contrast and noncontrast CBCTs were obtained in 7 patients. Intravenous-CBCT improved hepatic tumor visibility in breath-hold scans only for 3 patients (2 metastases, 1 hepatocellular carcinoma). Visible tumors ranged in volume from 124 to 564 mL. Small tumors in free-breathing patients did not show enhancement on IVCBT. Conclusions Intravenous-CBCT may enhance the visibility of hepatic vessels and tumor in CBCT scans obtained during breath hold. Optimization of IV contrast timing and reduction of artifacts to improve tumor visualization warrant further investigation.

An analysis of appropriate delivery of postoperative radiation therapy for endometrial cancer using the RAND/UCLA Appropriateness Method: Executive summary.

Abstract: Purpose To summarize the results of American Society for Radiation Oncology (ASTRO)’s analysis of appropriate delivery of postoperative radiation therapy (RT) for endometrial cancer using the RAND/University of California, Los Angeles (UCLA) Appropriateness Method, outline areas of convergence and divergence with the 2014 ASTRO endometrial Guideline, and highlight where this analysis provides new information or perspective. Methods and materials The RAND/UCLA Appropriateness Method was used to combine available evidence with expert opinion. A comprehensive literature review was conducted and a multidisciplinary panel rated the appropriateness of RT options for different clinical scenarios. Treatments were categorized by the median rating as Appropriate, Uncertain, or Inappropriate. Results The ASTRO endometrial Guideline and this analysis using the RAND/UCLA Appropriateness Method did not recommend adjuvant RT for early-stage, low-risk endometrioid cancers and largely agree regarding use of vaginal brachytherapy for low-intermediate and high-intermediate risk patients. For more advanced endometrioid cancer, chemotherapy with RT is supported by both documents. The Guideline and the RAND/UCLA analysis diverged regarding use of pelvic radiation. For stages II and III, this analysis rated external beam RT plus vaginal brachytherapy Appropriate, whereas the Guideline preferred external beam alone. In addition, this analysis offers insight on the role of histology, extent of nodal dissection, and para-aortic nodal irradiation; the use of intensity modulated RT; and management of stage IVA. Conclusions This analysis based on the RAND/UCLA Method shows significant agreement with the 2014 endometrial Guideline. Areas of divergence, often in scenarios with low-level evidence, included use of external beam RT plus vaginal brachytherapy in stages II and III and external beam RT alone in early-stage patients. Furthermore, the analysis explores other important questions regarding management of this disease site.