Pre-treatment factors associated with detecting additional brain metastases at stereotactic radiosurgery.

The number of brain metastases identified on diagnostic magnetic resonance imaging (MRI) is a key factor in consideration of stereotactic radiosurgery (SRS). However, additional lesions are often detected on high-resolution SRS-planning MRI. We investigated pre-treatment clinical characteristics that are associated with finding additional metastases at SRS. Patients treated with SRS for brain metastases between the years of 2009-2014 comprised the study cohort. All patients underwent frame-fixed, 1 mm thick MRI on the day of SRS. Patient, tumor, and treatment characteristics were analyzed for an association with increase in number of metastases identified on SRS-planning MRI. 289 consecutive SRS cases were analyzed. 725 metastases were identified on pre-treatment MRI and 1062 metastases were identified on SRS-planning MRI. An increase in the number of metastases occurred in 34 % of the cases. On univariate analysis, more than four metastases and the diameter of the largest lesion were significantly associated with an increase in number of metastases on SRS-planning MRI. When stratified by the diameter of the largest lesion into <2, 2-3, or ≥3 cm, additional metastases were identified in 37, 29, and 18 %, respectively. While this increase in the number of metastases is largely due to the difference in imaging technique, the number and size of the metastases were also associated with finding additional lesions. These clinical factors may be considered when determining treatment options for brain metastases.

A retrospective analysis of tumor volumetric responses to five-fraction stereotactic radiotherapy for paragangliomas of the head and neck (glomus tumors).

BACKGROUND: Skull base paragangliomas (SBP) are locally expansile tumors that can be treated with stereotactic radiotherapy with favorable results. This report describes the results of 31 patients with SBP treated with CyberKnife radiotherapy delivering a total dose of 25 Gray in five fractions. METHODS: All patients treated with five-fraction CyberKnife radiotherapy at a single institution were identified between 2007 and 2013. Tumor volumetric analyses were performed to assess responses to radiotherapy. RESULTS: Median follow-up was 24 months with a range of 4-78 months. Local control and overall survival were 100%. Of the 20 patients who presented with tinnitus, 12 reported improvement (60%), of whom 6 reported complete resolution. There was a 37.3% reduction in tumor volume among all patients (p = 0.16). On subset analysis of patients with ≥24 months of follow-up, tumor volume decreased 49% (p = 0.01). The rate of grade 1-2 toxicity was 19%, with no grade 3 or worse toxicity. CONCLUSION: A five-fraction CyberKnife-based stereotactic radiotherapy approach is safe and efficacious for the management for patients with SBP. Our findings suggest the potential use of this strategy as a definitive or salvage treatment option for SBP.

Timing of Surgery and Social Determinants of Health Related to Pathologic Complete Response after Total Neoadjuvant Therapy for Rectal Adenocarcinoma: Retrospective Study of National Cancer Database.

Total neoadjuvant therapy (TNT) for rectal adenocarcinoma (RAC) involves multi-agent chemotherapy and radiation before definitive surgery. Previous studies of the rest period (time between radiation and surgery) and pathologic complete response (pCR) have produced mixed results. The objective of this study was to evaluate the relationship between the rest period and pCR. This study utilized the National Cancer Database (NCDB) to retrospectively analyze 5997 stage-appropriate RAC cases treated with TNT from 2016 to 2020. The overall pCR rate was 18.6%, with most patients undergoing induction chemotherapy followed by long-course chemoradiation (81.5%). Multivariable logistic regression models revealed a significant non-linear relationship between the rest period and pCR (p = 0.033), with optimal odds at 14.7-15.9 weeks post radiation (odds ratio: 1.49, 95% confidence interval: 1.13-1.98) when compared to 4.0 weeks. Medicaid, distance to the treatment facility, and community education were associated with decreased odds of pCR. Findings highlight the importance of a 15-16-week post-radiation surgery window for achieving pCR in RAC treated with TNT and socioeconomic factors influencing pCR rates. Findings also emphasize the need for clinical trials to incorporate detailed analyses of the rest period and social determinant of health to better guide clinical practice.

Total skin electron beam radiation in a pediatric patient with leukemia cutis: a case report.

Leukemia cutis, a form of extramedullary leukemia involving the skin, is a poor prognostic marker and indicator of imminent hematologic relapse and chemotherapeutic resistance in leukemia patients. Although total skin electron beam radiotherapy is commonly recommended for patients with leukemia cutis, its role and effectiveness remains unclear. Here we describe a 19-month-old infant with acute myelogenous leukemia first diagnosed at 15 months of age. It relapsed in her skin at 18 months of age, associated with raised hyperpigmented lesions on her chest and scalp. Radiation treatment to the total skin surface with radiation therapy resulted in relief of her symptoms before relapse in the bone marrow.

Volumetric Modulated Arc Therapy Enabled Total Body Irradiation (VMAT-TBI): Six-year Clinical Experience and Treatment Outcomes.

Total body irradiation is an important part of the conditioning regimens frequently used to prepare patients for allogeneic hematopoietic stem cell transplantation (SCT). Volumetric-modulated arc therapy enabled total body irradiation (VMAT-TBI), an alternative to conventional TBI (cTBI), is a novel radiotherapy treatment technique that has been implemented and investigated in our institution. The purpose of this study is to (1) report our six-year clinical experience in terms of treatment planning strategy and delivery time and (2) evaluate the clinical outcomes and toxicities in our cohort of patients treated with VMAT-TBI. This is a retrospective single center study. Forty-four patients at our institution received VMAT-TBI and chemotherapy conditioning followed by allogeneic SCT between 2014 and 2020. Thirty-two patients (73%) received standard-dose TBI (12-13.2 Gy in 6-8 fractions twice daily), whereas 12 (27%) received low-dose TBI (2-4 Gy in one fraction). Treatment planning, delivery, and treatment outcome data including overall survival (OS), relapse-free survival (RFS), and toxicities were analyzed. The developed VMAT-TBI planning strategy consistently generated plans satisfying our dose constraints, with planning target volume coverage >90%, mean lung dose ∼50% to 75% of prescription dose, and minimal hotspots in critical organs. Most of the treatment deliveries were <100 minutes (range 33-147, mean 72). The median follow-up was 26 months. At the last follow-up, 34 of 44 (77%) of patients were alive, with 1- and 2-year OS of 90% and 79% and RFS of 88% and 71%, respectively. The most common grade 3+ toxicities observed were mucositis (31 patients [71%]) and nephrotoxicity (6 patients [13%]), both of which were deemed multifactorial in cause. Four patients (9%) in standard-dose cohort developed grade 3+ pneumonitis, with 3 cases in the setting of documented respiratory infection and only 1 (2%) deemed likely related to radiation alone. VMAT-TBI provides a safe alternative to cTBI. The dose modulation capability of VMAT-TBI may lead to new treatment strategies, such as simultaneous boost and further critical organ sparing, for better malignant cell eradication, immune suppression, and lower toxicities.

Phase I dose-escalation study of stereotactic body radiotherapy in patients with hepatic metastases.

PURPOSE: To identify a tolerable and effective dose for 5-fraction stereotactic body radiotherapy for hepatic metastases. METHODS: Patients were enrolled onto three dose-escalation cohorts: 30 Gy in 3 fractions, 50 Gy in 5 fractions, and 60 Gy in 5 fractions. Eligible patients had one to five hepatic metastases, ability to spare a critical hepatic volume (volume receiving <21 Gy) of 700 ml, adequate baseline hepatic function, no concurrent antineoplastic therapy, and a Karnofsky performance score of ≥60. Dose-limiting toxicity included treatment-related grade 3 toxicity in the gastrointestinal, hepatobiliary/pancreas, and metabolic/laboratory categories. Any grade 4 or 5 event attributable to therapy was defined as a dose-limiting toxicity. Local control (LC) and complete plus partial response rates were assessed. RESULTS: Twenty-seven patients, 9 in each cohort, with 37 lesions were enrolled and treated: 17 men and 11 women; median age 62 (range 48-86) years; most common site of primary disease, colorectal (44.4%). Median follow-up was 20 (range 4-53) months. There was no grade 4 or 5 toxicity or treatment-related grade 3 toxicity. Actuarial 24-month LC rates for the 30-, 50-, and 60-Gy cohorts were 56%, 89%, and 100%, respectively. There was a statistically significant difference for LC between the 60- and 30-Gy cohorts (P = 0.009) but not between the 60- and 50-Gy cohorts (P = 0.56) or the 50- and 30-Gy cohorts (P = 0.091). The maximum tolerated dose was not reached. CONCLUSIONS: A dose of 60 Gy in 5 fractions can be safely delivered to selected patients with hepatic metastases as long as the critical liver volume is respected. A dose of 60 Gy in 5 fractions yields an excellent level of LC.

Review of Biological Effects of Acute and Chronic Radiation Exposure on Caenorhabditis elegans.

Knowledge regarding complex radiation responses in biological systems can be enhanced using genetically amenable model organisms. In this manuscript, we reviewed the use of the nematode, Caenorhabditis elegans (C. elegans), as a model organism to investigate radiation's biological effects. Diverse types of experiments were conducted on C. elegans, using acute and chronic exposure to different ionizing radiation types, and to assess various biological responses. These responses differed based on the type and dose of radiation and the chemical substances in which the worms were grown or maintained. A few studies compared responses to various radiation types and doses as well as other environmental exposures. Therefore, this paper focused on the effect of irradiation on C. elegans, based on the intensity of the radiation dose and the length of exposure and ways to decrease the effects of ionizing radiation. Moreover, we discussed several studies showing that dietary components such as vitamin A, polyunsaturated fatty acids, and polyphenol-rich food source may promote the resistance of C. elegans to ionizing radiation and increase their life span after irradiation.

Effect of chemoradiation on the size of the thyroid gland.

We aimed to evaluate changes in thyroid gland size during the treatment of malignancies outside the head and neck with chemotherapy and/or external beam radiation. We performed a retrospective review of records of adult patients treated at our institution with external beam radiation to the chest and/or chemotherapy with taxanes, alkylating agents, and/or a topoisomerase II inhibitor. Neck and chest computed tomography (CT) images were used to calculate thyroid gland volume before and after therapy, using Vitrea® software or the volumetric ellipsoid method. Thirty-seven patients were included. After treatment, there was a significant reduction in thyroid gland volume of 14.0% (P < 0.01) using Vitrea and 17.1% (P < 0.05) using the volumetric ellipsoid method. Exposure to radiation or chemotherapy was not found to be associated with the degree of thyroid gland reduction, nor was the number of days between CT scans or the stage of the malignancy being treated. Finally, the degree of thyroid gland size reduction did not predict mortality. Our results showed that the treatment of malignancies outside the head and neck with chemotherapy and/or external beam radiation results in a reduction in thyroid gland size. The impact on thyroid gland function remains unknown.

Margin-Free Fractionated Stereotactic Radiation Therapy for Pediatric Brain Tumors.

PURPOSE: Conventional radiation therapy (RT) to pediatric brain tumors exposes a large volume of normal brain to unwarranted radiation causing late toxicity. We hypothesized that in well demarcated pediatric tumors lacking microscopic extensions, fractionated stereotactic RT (SRT), without target volume expansions, can reduce high dose normal tissue irradiation without affecting local control. METHODS AND MATERIALS: Between 2008 and 2017, 52 pediatric patients with brain tumors were treated using the CyberKnife (CK) with SRT in 180 to 200 cGy per fraction. Thirty representative cases were retrospectively planned for intensity modulated RT (IMRT) with 4-mm PTV expansion. We calculated the volume of normal tissue within the high or intermediate dose region adjacent to the target. Plan quality and radiation dose-volume dosimetry parameters were compared between CK and IMRT plans. We also reported overall survival, progression-free survival (PFS), and local control. RESULTS: Tumors included low-grade gliomas (n = 28), craniopharyngiomas (n = 16), and ependymomas (n = 8). The volumes of normal tissue receiving high (≥80% of prescription dose or ≥40 Gy) or intermediate (80% > dose ≥50% of the prescription dose or 40 Gy > dose ≥25 Gy) dose were significantly smaller with CK versus IMRT plans (P < .0001 for all comparisons). With a median follow-up of 3.7 years (range, 0.1-9.0), 3-year local control was 92% for all patients. Eight failures occurred: 1 craniopharyngioma (marginal), 2 ependymomas (both in-field), and 5 low-grade gliomas (2 in-field, 1 marginal, and 2 distant). CONCLUSIONS: Fractionated SRT using CK without target volume expansion appears to reduce the volume of irradiated tissue without majorly compromising local control in pediatric demarcated brain tumors. These results are hypothesis generating and should be tested and validated in prospective studies.

Phase II trial of hippocampal-sparing whole brain irradiation with simultaneous integrated boost for metastatic cancer.

BACKGROUND: Advanced radiotherapeutic treatment techniques limit the cognitive morbidity associated with whole-brain radiotherapy (WBRT) for brain metastasis through avoidance of hippocampal structures. However, achieving durable intracranial control remains challenging. METHODS: We conducted a single-institution single-arm phase II trial of hippocampal-sparing whole brain irradiation with simultaneous integrated boost (HSIB-WBRT) to metastatic deposits in adult patients with brain metastasis. Radiation therapy consisted of intensity-modulated radiation therapy delivering 20 Gy in 10 fractions over 2-2.5 weeks to the whole brain with a simultaneous integrated boost of 40 Gy in 10 fractions to metastatic lesions. Hippocampal regions were limited to 16 Gy. Cognitive performance and cancer outcomes were evaluated. RESULTS: A total of 50 patients, median age 60 years (interquartile range, 54-65), were enrolled. Median progression-free survival was 2.9 months (95% CI: 1.5-4.0) and overall survival was 9 months. As expected, poor survival and end-of-life considerations resulted in a high exclusion rate from cognitive testing. Nevertheless, mean decline in Hopkins Verbal Learning Test-Revised delayed recall (HVLT-R DR) at 3 months after HSIB-WBRT was only 10.6% (95% CI: -36.5‒15.3%). Cumulative incidence of local and intracranial failure with death as a competing risk was 8.8% (95% CI: 2.7‒19.6%) and 21.3% (95% CI: 10.7‒34.2%) at 1 year, respectively. Three grade 3 toxicities consisting of nausea, vomiting, and necrosis or headache were observed in 3 patients. Scores on the Multidimensional Fatigue Inventory 20 remained stable for evaluable patients at 3 months. CONCLUSIONS: HVLT-R DR after HSIB-WBRT was significantly improved compared with historical outcomes in patients treated with traditional WBRT, while achieving intracranial control similar to patients treated with WBRT plus stereotactic radiosurgery (SRS). This technique can be considered in select patients with multiple brain metastases who cannot otherwise receive SRS.

A Phase 2 Clinical Trial of SABR Followed by Immediate Vertebroplasty for Spine Metastases.

PURPOSE: To determine the pain response and prevention of vertebral compression fractures (VCFs) after single-fraction stereotactic ablative radiation therapy (SABR) in conjunction with immediate vertebroplasty for spine metastases. METHODS AND MATERIALS: Patients with localized spine metastases free from VCF associated with loss of vertebral height with a pain score ≥4 using the visual analog scale were enrolled. Spine SABR was performed with 20 Gy delivered to the gross disease and 14 Gy to the contiguous bone marrow in a single fraction. Immediate, prophylactic vertebroplasty was performed within 1 month after spine SABR. The primary endpoint was pain response at 3 months compared to the historical control with external beam radiation therapy from Radiation Therapy Oncology Group study 9714. Secondary endpoints included pain response at 1 month, duration of pain response, vertebroplasty rate, VCF rate, local control, and overall survival. RESULTS: Thirty-five patients were enrolled, of whom 29 were deemed eligible and underwent single-fraction spine SABR. Twenty-three of these patients subsequently underwent prophylactic vertebroplasty. The 3-month pain response was significantly improved compared to Radiation Therapy Oncology Group study 9714: 95% versus 51% (P < .0001). The local control with a median follow-up of 9.6 months was 92%. The freedom from VCF was 90% at 1 year. Spine SABR was well tolerated with no grade 2 or higher toxicities. A single patient with disease extending from the vertebral body into the spinal canal developed vertebroplasty-related myelopathy, which was corrected with surgery. CONCLUSIONS: Single-fraction SABR immediately followed by prophylactic vertebroplasty improves pain response compared with conventional radiation therapy while providing long-term pain control and structural stability of the treated spine. Vertebroplasty is well tolerated as a prophylactic measure in patients without loss of vertebral height after spine SABR. Pain response and VCF rates are similar to patients undergoing SABR alone. Thus, patients who would benefit most from the addition of vertebroplasty need to be further identified.

Four-dimensional computed tomography scan analysis of tumor and organ motion at varying levels of abdominal compression during stereotactic treatment of lung and liver.

PURPOSE: To investigate the effectiveness of different abdominal compression levels on tumor and organ motion during stereotactic body radiotherapy of lower lobe lung and liver tumors using four-dimensional (4D)-CT scan analysis. METHODS AND MATERIALS: Three 4D-CT scans were acquired for 10 patients first using with no compression and then compared with two different levels of abdominal compression. The position of the tumor and various organs were defined at the peak inspiratory and expiratory phases and compared to determine the maximum motion. RESULTS: Mean (+/-SD) medium compression force (MC) and high compression force (HC) were 47.6 +/- 16.0 N and 90.7 +/- 27.1 N, respectively. Mean overall tumor motion was 13.6 mm (2sigma [2 sigma] 11.5-15.6), 8.3 mm (2sigma 6.0-10.5), and 7.2 mm (2sigma 5.4-9.0) for no compression, MC, and HC, respectively. A significant difference in the control of both superior-inferior (SI) and overall motion of tumors was seen with the application of MC and HC when compared with no compression (p < 0.0001 for both). High compression force improved SI and overall tumor motion compared with MC, but this was only significant for SI motion (p = 0.04 and p = 0.06). Significant control of organ motion was only seen in the pancreas (p = 0.01). CONCLUSIONS: Four-dimensional CT shows significant control of both lower lobe lung and liver tumors using abdominal compression. High levels of compression improve SI tumor motion when compared with MC.

Optimizing dose and fractionation for stereotactic body radiation therapy. Normal tissue and tumor control effects with large dose per fraction.

Stereotactic body radiation therapy (SBRT) is a potent noninvasive means of administering high-dose radiation to demarcated tumor deposits in extracranial locations. The treatments use image guidance and related treatment delivery technology for the purpose of escalating the radiation dose to the tumor itself with as little radiation dose to the surrounding normal tissue as possible. The local tumor control for SBRT has been higher than anything previously published for radiotherapy in treating typical carcinomas. In addition, the pattern, timing and severity of toxicity have been very different than what was seen with conventional radiotherapy. In this review, the clinical characteristics and outcomes of SBRT are presented in the context of their underlying mechanisms. While much of the material is unproven and speculative, it at least qualitatively searches for understanding as to the biological basis for the observed clinical effects. Hopefully, it will serve as a motivation for more sophisticated biological research into the effects of SBRT.

Lung cancer: a model for implementing stereotactic body radiation therapy into practice.

Primary and metastatic tumors to the lung have been principle targets for the noninvasive high-doseper- fraction treatment programs now officially called stereotactic body radiation therapy (SBRT). Highly focused treatment delivery to moving lung targets requires accurate assessment of tumor position throughout the respiratory cycle. Measures to account for this motion, either by tracking (chasing), gating, or inhibition (breath hold and abdominal compression) must be employed in order to avoid large margins of error that would expose uninvolved normal tissues. The treatments use image guidance and related treatment delivery technology for the purpose of escalating the radiation dose to the tumor itself with as little radiation dose to the surrounding normal tissues as possible. Clinical trials have demonstrated superior local control with SBRT as compared with conventionally fractionated radiotherapy. While late toxicity requires further careful assessment, acute and subacute toxicity are remarkably infrequent. Radiographic and local tissue effects consistent with bronchial damage and downstream collapse with fibrosis are common, especially with adequate doses capable of ablating tumor targets. As such, great care must be taken when employing SBRT near the serially functioning central chest structures including the esophagus and major airways. While mechanisms of this injury remain elusive, ongoing prospective trials offer the hope of finding the ideal application for SBRT in treating pulmonary targets.

Multistage stereotactic radiosurgery for large cerebral arteriovenous malformations using the Gamma Knife platform.

PURPOSE: Radiosurgery is an established technique to treat cerebral arteriovenous malformations (AVMs). Obliteration of larger AVMs (> 10-15 cm3 or diameter > 3 cm) in a single session is challenging with current radiosurgery platforms due to toxicity. We present a novel technique of multistage stereotactic radiosurgery (SRS) for large intracranial arteriovenous malformations (AVM) using the Gamma Knife system. MATERIALS/METHODS: Eighteen patients with large (> 10-15 cm3 or diameter > 3 cm) AVMs, which were previously treated using a staged SRS technique on the Cyberknife platform, were retrospectively selected for this study. The AVMs were contoured and divided into 3-8 subtargets to be treated sequentially in a staged approach at half to 4 week intervals. The prescription dose ranged from 15 Gy to 20 Gy, depending on the subtarget number, volume, and location. Gamma Knife plans using multiple collimator settings were generated and optimized. The coordinates of each shot from the initial plan covering the total AVM target were extracted based on their relative positions within the frame system. The shots were regrouped based on their location with respect to the subtarget contours to generate subplans for each stage. The delivery time of each shot for a subtarget was decay corrected with 60 Co for staging the treatment course to generate the same dose distribution as that planned for the total AVM target. Conformality indices and dose-volume analysis were performed to evaluate treatment plans. RESULTS: With the shot redistribution technique, the composite dose for the multistaged treatment of multiple subtargets is equivalent to the initial plan for total AVM target. Gamma Knife plans resulted in an average PTV coverage of 96.3 ± 0.9% and a PITV of 1.23 ± 0.1. The resulting Conformality indices, V12Gy and R50 dose spillage values were 0.76 ± 0.05, 3.4 ± 1.8, and 3.1 ± 0.5 respectively. CONCLUSION: The Gamma Knife system can deliver a multistaged conformal dose to treat large AVMs when correcting for translational setup errors of each shot at each staged treatment.

Phantom-to-clinic development of hypofractionated stereotactic body radiotherapy for early-stage glottic laryngeal cancer.

The purpose of this study was to commission and clinically test a robotic stereotactic delivery system (CyberKnife, Sunnyvale, CA) to treat early-stage glottic laryngeal cancer. We enrolled 15 patients with cTis-T2N0M0 carcinoma of the glottic larynx onto an institutional review board (IRB)-approved clinical trial. Stereotactic body radiotherapy (SBRT) plans prescribed 45 Gy/10 fractions to the involved hemilarynx. SBRT dosimetry was compared with (1) standard carotid-sparing laryngeal intensity-modulated radiation therapy (IMRT) and (2) selective hemilaryngeal IMRT. Our results demonstrate that SBRT plans improved sparing of the contralateral arytenoid (mean 20.0 Gy reduction, p <0.001), ipsilateral carotid Dmax (mean 20.6 Gy reduction, p <0.001), contralateral carotid Dmax (mean 28.1 Gy reduction, p <0.001), and thyroid Dmean (mean 15.0 Gy reduction, p <0.001) relative to carotid-sparing IMRT. SBRT also modestly improved dose sparing to the contralateral arytenoid (mean 4.8 Gy reduction, p = 0.13) and spinal cord Dmax (mean 4.9 Gy reduction, p = 0.015) relative to selective hemilaryngeal IMRT plans. This "phantom-to-clinic" feasibility study confirmed that hypofractionated SBRT treatment for early-stage laryngeal cancer can potentially spare dose to adjacent normal tissues relative to current IMRT standards. Clinical efficacy and toxicity correlates continue to be collected through an ongoing prospective trial.

Remote location interstitial brachytherapy with patient stabilization and subsequent transport to an outpatient center for treatment is safe and effective for the treatment of gynecologic malignancies.

PURPOSE: Interstitial brachytherapy is an essential component of definitive treatment for locally advanced gynecological malignancies. Although many outpatient centers are capable of delivering the radiation component of brachytherapy, they are not associated with an operative center for implant placement, limiting the ability to deliver appropriate care. In this study, we report on our experience with noncolocated implant placement and radiation delivery, and the impact of patient stabilization improvements on patient safety. METHODS AND MATERIALS: Between 9/2010 and 11/2014, 25 patients with gynecologic malignancy underwent interstitial implantation and subsequent transport for high-dose-rate brachytherapy treatment. From 9/2010 to 10/2012, patients were transported using a standard ambulance stretcher; from 11/2012 to 11/2014, patients were placed on a patient positioning board or a WAFFLE support. Potential transport-associated toxicity was assessed, and the association between standard and augmented transport types and toxicity was analyzed. RESULTS: A total of 234 transports were performed. Median cost of transport was $150 per transport. There were 14 (10 patients) potential transportation-associated toxicities, including two lacerations/local trauma, three infections, and nine ulcers. There were 6 Grade 3 toxicities, all in the standard group. There was no association between stretcher type and laceration or ulcers, but enhanced support was associated with fewer overall toxicities, Grade 3 toxicities, and infections. CONCLUSIONS: Noncolocated implantation and treatment is safe and facilitates optimal therapy. Toxicities potentially associated with transport are minimal and seem to be reduced by augmented stabilization. Understanding that this is a reasonable way to deliver brachytherapy may allow more stand-alone centers to deliver high-quality care for patients and improve gynecologic cancer outcomes in the United States.

Automatic metastatic brain tumor segmentation for stereotactic radiosurgery applications.

The objective of this study is to develop an automatic segmentation strategy for efficient and accurate metastatic brain tumor delineation on contrast-enhanced T1-weighted (T1c) magnetic resonance images (MRI) for stereotactic radiosurgery (SRS) applications. The proposed four-step automatic brain metastases segmentation strategy is comprised of pre-processing, initial contouring, contour evolution, and contour triage. First, T1c brain images are preprocessed to remove the skull. Second, an initial tumor contour is created using a multi-scaled adaptive threshold-based bounding box and a super-voxel clustering technique. Third, the initial contours are evolved to the tumor boundary using a regional active contour technique. Fourth, all detected false-positive contours are removed with geometric characterization. The segmentation process was validated on a realistic virtual phantom containing Gaussian or Rician noise. For each type of noise distribution, five different noise levels were tested. Twenty-one cases from the multimodal brain tumor image segmentation (BRATS) challenge dataset and fifteen clinical metastases cases were also included in validation. Segmentation performance was quantified by the Dice coefficient (DC), normalized mutual information (NMI), structural similarity (SSIM), Hausdorff distance (HD), mean value of surface-to-surface distance (MSSD) and standard deviation of surface-to-surface distance (SDSSD). In the numerical phantom study, the evaluation yielded a DC of 0.98 ± 0.01, an NMI of 0.97 ± 0.01, an SSIM of 0.999 ± 0.001, an HD of 2.2 ± 0.8 mm, an MSSD of 0.1 ± 0.1 mm, and an SDSSD of 0.3 ± 0.1 mm. The validation on the BRATS data resulted in a DC of 0.89 ± 0.08, which outperform the BRATS challenge algorithms. Evaluation on clinical datasets gave a DC of 0.86 ± 0.09, an NMI of 0.80 ± 0.11, an SSIM of 0.999 ± 0.001, an HD of 8.8 ± 12.6 mm, an MSSD of 1.5 ± 3.2 mm, and an SDSSD of 1.8 ± 3.4 mm when comparing to the physician drawn ground truth. The result indicated that the developed automatic segmentation strategy yielded accurate brain tumor delineation and presented as a useful clinical tool for SRS applications.

Stereotactic radiation therapy of renal cancer inferior vena cava tumor thrombus.

Renal Cell Carcinoma (RCC) is a common malignancy world-wide that is rising in incidence. Up to 10% of RCC patients present with inferior vena cava (IVC) tumor thrombus (IVC-TT). Although surgery is the only treatment with proven efficacy for IVC-TT, the surgical management of advanced (level III and IV) IVC-TT is difficult with high morbidity and mortality, and offers a poor survival outcome. Currently, there are no treatment options in the setting of recurrent or unresectable RCC IVC-TT. Even though RCC may be resistant to conventionally fractionated radiation therapy, hypofractionated radiation has shown excellent control rates for both primary and metastatic RCC. We report our experience treating 2 RCC patients with Level IV IVC-TT -one recurrent and the other unresectable-with stereotactic ablative radiation therapy (SABR). The first patient is a 75-year-old gentleman with a level IV RCC IVC-TT who presented 9 months after his radical nephrectomy and thrombectomy with a growing level IV IVC-TT that became refractory to 4 targeted agents. He received SABR of 50Gy in 5 fractions and at 2-year follow-up is doing well with a significant decrease in the enhancement and size of the IVC-TT. The second patient is an 83-year-old gentleman who presented with metastatic RCC and level IV IVC-TT but was not a surgical candidate. After progression on temsirolimus, he received SABR of 36Gy in 4 fractions to his IVC-TT and survived 18 months post-SABR. Both patients improved symptomatically and did not experience any acute or late treatment-related toxicity. Their survival of 24 months and 18 months are comparable to the reported median survival of 20 months in patients with level IV IVC-TT that underwent surgical resection. Therefore, SABR can be a potentially safe treatment option in the unresectable setting for RCC patients with IVC-TT and should be further evaluated in prospective trials.

Phase II trial of stereotactic body radiation therapy combined with erlotinib for patients with limited but progressive metastatic non-small-cell lung cancer.

PURPOSE: Patients with stage IV non-small-cell lung cancer (NSCLC) who progress through first-line therapy have poor progression-free survival (PFS) and overall survival (OS), most commonly failing in original sites of gross disease. Cytoreduction with stereotactic body radiation therapy (SBRT) may help systemic agents delay relapse. PATIENTS AND METHODS: Patients in our single arm phase II study had stage IV NSCLC with no more than six sites of extracranial disease who failed early systemic chemotherapy and were able to receive SBRT and concurrent erlotinib until disease progression. After erlotinib commencement, SBRT with equipotent fractionation was delivered to all sites of disease. PFS, OS, and other end points were evaluated. RESULTS: Twenty-four patients (13 men and 11 women) with a median age of 67 years (range, 56-86 years) were enrolled with median follow-up of 11.6 months. All patients had progressed through platinum-based chemotherapy. A total of 52 sites were treated with 16 of 24 patients receiving SBRT to more than one site. Lung parenchyma was most often irradiated. Median PFS was 14.7 months, and median OS was 20.4 months. Most patients progressed in new distant sites with only three of 47 measurable lesions recurring within the SBRT field. Two grade 3 toxicities were radiation related. Zero of 13 patients tested were positive for an EGFR mutation. CONCLUSION: Use of SBRT with erlotinib for unselected patients with stage IV NSCLC as a second- or subsequent line therapy resulted in dramatic changes in patterns of failure, was well tolerated, and resulted in high PFS and OS, substantially greater than historical values for patients who only received systemic agents.