As a possible therapeutic approach robotic stereotactic ablative radiotherapy (SABR) is currently under investi- gation as a non-invasive treatment option for patients with RCC. Renal cell carcinoma is frequently reported as a radio-resistant tumor. However, pathologic complete responses have been described after ablative radiother- apy previously . Tumor motion and the need for high ablative radiation doses while preserving the remaining renal parenchyma, poses a major challenge. Robotic ra- diosurgery allows continuous tumor tracking under free breathing and therefore minimal gross tumor volume (GTV) to planning target volume (PTV) margins are needed. Robotic SABR for moving tumors is already established as a standard treatment option for patients with early stage non-small cell lung cancer [3, 4].
We searched PubMed, Embase, and the Wiley Online Library for eligible studies published before January 1, 2017. The following groups of key words or medical terms were used: (“stereotactic body radiotherapy” or “stereotactic ablative radiotherapy” or “SBRT” or “SABR”) and (“surgery” or “operation” or “lobectomy” or “sublobar resection” or “limited resection” or “sublobectomy” or “segmentectomy” or “wedge resection”) and (“non-small cell lung cancer” or “non-small cell lung carcinoma” or “non-small cell lung neoplasms” or “lung adenocarcinoma” or “lung squamous cell carcinoma” or “large cell lung cancer”). Only articles in English were selected. Furthermore, reference lists of relevant studies were searched for potentially eligible records.
Thirdly, we did not assess the impact of neutron contamination on second cancer risks for the 10 MV plan. It has previously been demonstrated, however, that at 10 MV this effect is very small (Kry et al 2005a). Fourthly, only three patients’ pelvic CT scans were evaluated for in-field and close-to-field second cancer risks, and only one was evaluated for out-of-field risks. Similar to this study, the majority of prostate cancer planning studies which evaluate radiation-induced second cancer risks in a series of adult patients, all planned using the same variety of techniques, do so in one to three patients. The reason for the small sample size is that the primary interest is differences between techniques rather than inter-patient variabil- ity (Kry et al 2005b, 2010, Schneider 2006, Stathakis et al 2007, Ruben et al 2008, Fontenot et al 2009, Bednarz et al 2010, Kragl et al 2011, Blais et al 2012, Rechner et al 2012) A few studies have, however, compared up to 10 patients, each planned using the same variety of techniques (Fontenot et al 2010, Patil et al 2010, Yoon et al 2010). Dasu et al (2011), how- ever, aimed to evaluate inter-patient variability in second cancer risk and so included 100 patients, each planned using SABR and conventionally fractionated radiotherapy, although this analysis was restricted to rectal and bladder DVH analysis, and did not include out-of- field dose measurements. Given the relative anatomical constancy of the prostate in relation to organs-at-risk, however, any variability in second cancer risk is likely to be less than what might be expected for tumours with greater variability in location, suggesting that a low number of patients may be acceptable. This is reinforced by the consistency in results for the three evaluated patients, thus adding confidence to our use of a small patient sample. For out-of-field organs, minimal variation in dose between patients would be expected, and so the use of one patient, planned in several different ways, is adequate for comparison of dif- ferent techniques.
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The primary goal of this thesis was to investigate response to SABR using DCE-MRI at an early timepoint post SABR in early stage breast cancer patients. However, before this could be investigated, it was necessary to address two issues related to the acquisition and analysis of DCE-MRI. First, contrast agent safety issues lead to a temporary halt to the post- SABR imaging in SIGNAL. We decided to reduce the contrast agent dose that patients would receive to half the standard clinical dose. While the radiation oncologists involved in SIGNAL found that using the reduced dose of contrast agent the tumour conspicuity was su ffi cient for radiotherapy planning, nevertheless, we wanted to quantitatively investigate what e ff ect this reduced dose would have on target volume delineation for MRI guided radiotherapy planning. Second, we wished to quantify the e ff ect that registration had on parameter values, precision, and model goodness of fit from application of the commonly used Tofts model. Finally, we also considered the e ff ect of strategies to reduce computation time and how it a ff ected these same parameters.
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Cancer is the leading cause of death worldwide, with non-small cell lung cancer (NSCLC) being the most common cause of cancer related mortality 1 . In the treatment of early-stage NSCLC, surgical resection is considered the standard of care 2 . However, some patients are deemed medically inoperable due to age, decreased pulmonary reserve, cardiac function, or significant co-morbidities 3 . Medically inoperable patients, as well as patients unwilling to undergo surgery, have the option to be treated using stereotactic ablative radiotherapy (SABR). SABR is a hypofractionated technique where a very high ablative dose per treatment is delivered in few fractions, normally three to eight. Therefore, tumor conformality and sparing of normal tissue is increasingly crucial with SABR in comparison to conventional fractionation. SABR treatments are computed using multiple beam angles to achieve sharp dose gradients needed to spare healthy tissue. Outcome studies have shown SABR has an overall survival of 41.2% compared to 66.1% for patients who undergo lobectomy at five years, meanwhile, local control at three years has improved with SABR, 87.8%, compared to lobectomy resection, 85% 2 .
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A number of prospective trials are ongoing in this area. The Stereotactic Ablative Radiotherapy for Oligometa- static Non-small Cell Lung Cancer (SARON: NCT02417662) randomised controlled trial commenced recruitment in early 2016 and will determine the impact on overall survival of RT (both conventional and SABR) used alongside conventional chemotherapy in the first-line treatment of synchronous oligometastatic disease. In con- trast, the phase II/III Conventional Care Versus Radioab- lation for Extracranial Metastases (CORE: NCT02759783) trial will evaluate SABR used in metachronous oligome- tastatic disease arising from NSCLC, breast cancer or prostate cancer. In the same setting, the Stereotactic Ablative Radiotherapy for Comprehensive Treatment of Oligometastatic Tumours (SABR-COMET: NCT01446744), which has now closed to recruitment will review the impact of SABR applied to metastatic lesions on both overall survival and quality of life.
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Abstract: Locally advanced pancreatic carcinoma (LAPC) has a poor prognosis and the purpose of treatment is survival prolongation and symptom palliation. Radiotherapy has been reported to reduce pain in LAPC. Stereotactic RT (SBRT) is considered as an emerging radiotherapy technique able to achieve high local control rates with acceptable toxicity. However, its role in pain palliation is not clear. To review the impact on pain relief with SBRT in LAPC patients, a literature search was performed on PubMed, Scopus, and Embase (January 2000–December 2017) for prospective and retrospective articles published in English. Fourteen studies (479 patients) reporting the effect of SBRT on pain relief were finally included in this analysis. SBRT was delivered with both standard and/or robotic linear accelerators. The median prescribed SBRT doses ranged from 16.5 to 45 Gy (median: 27.8 Gy), and the number of fractions ranged from 1 to 6 (median: 3.5). Twelve of the 14 studies reported the percentage of pain relief (in patients with pain at presentation) with a global overall response rate (complete and partial response) of 84.9% (95% CI, 75.8%–91.5%), with high heterogeneity (Q 2 test: P<0.001; I 2 =83.63%). All
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In radiotherapy, clinicians and researchers rely on translational studies performed on laboratory animals to investigate radiobiology hypothesis, test new biomarkers and develop novel therapeutics. Preferably, these studies should be performed on irradiators capable of delivering focal irradiation with image guidance [1, 2]. Thus far, two products have been commercialized for this purpose, including the SARRP system developed at Johns Hopkins University  and the X-Rad 225Cx system developed at Princess Margaret Hospital . Both systems utilize cone beam CT (CBCT) for target localization, and their introduction has already led to exciting findings in radiobiology studies [5, 6]. The CBCT on both commercial systems relies upon the traditional design of a rotating gantry which houses both an x-ray source and/or detector [1, 3, 4, 7]. The complexity of this design warrants nontrivial efforts for periodic calibration and maintenance. The cost of these systems can also be a prohibitive factor hindering their wide scale adoption.
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The first 50 patients included in the FLAME- trial, were treated between October 2009 and October 2010 at the Department of Radiation Oncology of the UMC Utrecht. All patients received seven-beam intensity-modulated radiotherapy (IMRT). A mean dose of 77 Gy in 35 frac- tion of 2.2 Gy was prescribed to the planning target volume (PTV) and at least 70 Gy was prescribed to 99% of the PTV [33,34]. The radiation margin around the prostate depends on several uncertainties in the daily clinical practice [55-57]. For our institute based on minimal positioning errors  and a simulation of their impact on dose coverage , a PTV margin of 4 mm was chosen. We aimed at limiting the dose to the rectum and bladder so that ≤ 5% of the rectum and ≤ 10% of the bladder receives a dose of ≥ 72 Gy. Further- more, a volume of 1 cc of the bladder and rectum receives a maximum dose of 80 Gy and 77 Gy, respec- tively, and ≤ 50% of the rectum receives a dose of ≥ 50 Gy . All treatment plans were checked by two inves- tigators (UAH and MV) before start of the treatment. The beam directions were 0º, 50º, 100º, 155º, 205º, 260º and 310º. The location of the fiducial markers was determined by visualizing the markers using portal images of the first segment of the 0º beam and the 260º beam. A difference of more than 1 mm compared to the planning-CT was corrected online. After 5 fractions the average rotation of the prostate was calculated. A rota- tion of 3º around the anterior-posterior or the left-right axis and a rotation of 6º around the cranio-caudal axis was corrected by changing the gantry or table rotation or the collimator angle. The portal images of the first segment of the remaining beams were used to deter- mine the average intrafraction prostate motion . For each patient the individual intrafraction and remaining rotational errors were used to calculate the actual deliv- ered doses to the target and the organs at risk.
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Importantly, the constraints presented in this document are intended for a first course of SABR to a previously non-irradiated site. For patients who have received previous radiotherapy, the uncertainties in re-irradiation normal tissue tolerance are substantial. SABR re-irradiation has, however, been successfully delivered to oligometastases, with encouraging rates of local control and low rates of high grade toxicity in small and heterogeneous series [45,46]. Most study to date has been devoted to the re-irradiation tolerance of the spinal cord, but even then, patient numbers are relatively low [46,47]. As such, determining SABR re-irradiation constraints is an area for future research and is beyond the scope of this current report.
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Stereotactic body radiotherapy (SBRT) is an attractive alternative to lobar resection in patients with early stage non-small-cell lung cancer (NSCLC) not eligible for lobec- tomy. Compared with surgery, SBRT is noninvasive; it does not involve postoperative complications and can realize good local control [1, 2]. Intensity-modulated radiother- apy (IMRT) and volumetric-modulated arc radiotherapy (VMAT) are typical technolo- gies used in NSCLC SBRT . IMRT enables good conformity to tumor volume and low doses for healthy tissues . Through the development of dynamic delivery using multi-leaf collimators (MLC), VMAT can deliver dose efficiently to reduce uncertainties in the intra-fraction setup [5, 6]. In IMRT, dose is delivered through a serial of static seg- ments which is made up of modulated MLCs’ shapes. IMRT employs variable intensity across multiple radiation beams leading to the construction of highly conformal dose distributions. VMAT is an advanced IMRT technology . The linac rotates around the patient and the MLCs continuously reshape and change the intensity of beams during dose delivery. Giving the radiotherapy in VMAT shortens the treatment time. VMAT is an alternative to fixed-gantry angle IMRT delivery. It allows the simultaneous varia- tion of gantry rotation speed, treatment aperture shape via movement of MLC leaves, and dose rate during treatment delivery. One of the most important factors that affects the prognosis of IMRT and VMAT is the quality of the treatment plan, which depends on the experience and skill of the planner [8, 9]. Moreover, a plan is often developed through trial-and-error, necessitating a long planning time, which can be a limitation.
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The first reported hypofractionated radiation therapy treatments for prostate cancer occurred in the early 1960’s . These treatments, delivering 6 fractions of 6 Gy to a total dose of 36 Gy, were motivated by resource limitations rather than radiobiology. Nevertheless, two decades of follow-up has confirmed that this regimen led to favorable local response, survival, and safety over the long term. Subsequently, hypofractionated prostate cancer treatment has been performed with EBRT in per- fraction doses ranging from 2.5 - 3.1 Gy [8-11], with brachytherapy (BT) in per-fraction doses of 5.5 - 11.5 Gy[12,13], and with linac-based stereotactic body radio- therapy (SBRT) using 5 fractions of 6.7 Gy . In a recent paper King et al. reported a median 33-month follow-up for patients that received 5 fractions of 7.25 Gy (total dose 36.25 Gy). They reported no biochemical failure with early and late toxicity profiles no worse than conventional EBRT . Thus, in relatively short-term follow-up, hypofractionated treatment of prostate cancer can result in effective biochemical control while main- taining low rectal and bladder toxicities.
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The patients were treated at the German Cancer Research Center (dkfz) in cooperation with the Radiological Clinic of the University of Heidelberg. MR and CT scans (only MR imaging data in the case of single-dose radiation therapy) were employed for three-dimensional treatment planning by means of Voxelplan (software developed at the dkfz) or STP (Leibin- ger; Freiburg, Germany). All patients were positioned in an individual head mask (14) and treated using a linear accelerator with 6 MeV or 15 MeV energy (Siemens Corporation, Con- cord, CA). Forty-eight patients with astrocytoma or oligoden- droglioma received fractionated stereotactic radiation therapy with single doses of 1.8 or 2 Gy and a median total dose at the isocenter of 55.8 Gy (range: 50.4–66 Gy). The 90% iso- dose surrounded the planning target volume (1).
The focus of many of these studies is the use of SABR in the treatment of oligometastatic disease. Inherent in the delivery of SABR to oligometastatic sites at any location in the body is an understanding of the local normal tissue dose constraints. It is recognised that as SABR is a relatively new treatment technique, definitively established dose constraints which directly correlate to risk of toxicity are rare. However, in order to standardise protocols and the associated radiotherapy planning, members of the various trial management groups collaborated to generate a consensus document on appropriate organ at risk (OAR) dose constraints associated with the various common SABR fractionations.
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Case presentation: An 83-year-old Asian man was diagnosed with T2N0M0 lung cancer in the form of squamous cell carcinoma in the lower lobe of his left lung. He was treated with stereotactic body radiotherapy of 40 Gy in 4 fractions and the tumor decreased in size in partial response. The local tumor recurred 8 months after the first stereotactic body radiotherapy, and he was re-irradiated with a second stereotactic body radiotherapy of 50 Gy in 4 fractions. A Sengstaken – Blakemore tube was inserted below his diaphragm by laparoscopic surgery before the second stereotactic body radiotherapy in order to reduce the stomach dose by keeping his stomach apart from the tumor. Two months after the second stereotactic body radiotherapy, he developed fatal gastric perforation and gastropleural fistula penetrating his diaphragm.
The single-isocenter technique in linear accelerator-based stereotactic radiosurgery/stereotactic body radiotherapy (SRS/SBRT) has been broadly used to treat multiple lesions. However, quantit- ative study to verify that the mechanical field center coincides with the radiation field center when both are off from the isocenter has never been performed. We developed an innovative method to measure this accuracy, called the off-isocenter Winston-Lutz test, and here we provided a practical clinical guideline to implement this technique. We used ImagePro V.6 to analyze images of a Wins- ton-Lutz phantom obtained using a Varian 21EX linear accelerator with an electronic portal imaging device, set up as for single-isocenter SRS/SBRT for multiple lesions. We investigated asymmetry field centers that were 3 cm and 5 cm away from the isocenter, as well as performing the standard Winston-Lutz test. We used a special beam configuration to acquire images while avoiding colli- sion, and we investigated both jaw and multileaf collimation. For the jaw collimator setting, at 3 cm off-isocenter, the mechanical field deviated from the radiation field by about 2.5 mm; at 5 cm, the deviation was above 3 mm, up to 4.27 mm. For the multileaf collimator setting, at 3 cm off- isocenter, the deviation was below 1 mm; at 5 cm, the deviation was above 1 mm, up to 1.72 mm, which was 72% higher than the tolerance threshold. These results indicated that the further the asymmetry field center is from the machine isocenter, the larger the deviation of the mechanical field from the radiation field, and the distance between the center of the asymmetry field and the isocenter should not exceed 3 cm in our clinic. We recommend that every clinic that uses linear ac- celerator, multileaf collimator-based SRS/SBRT perform the off-isocenter Winston-Lutz test in addi- tion to the standard Winston-Lutz test and use their own deviation data to create planning guideline.
Purpose and Method: A systematic literature review of six computerised databases was undertaken in order to review and summarise a forward planned lung stereotactic ablative body radiotherapy (SABR) treatment planning (TP) technique as a starting point for clinical implementation in the author ’ s department based on current empirical research. The data were abstracted and content analysed to synthesise the ﬁ ndings based upon a SIGN quality checklist tool.
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From March 2012 to April 2014, 18 patients with 22 lesions were enrolled. Table 1 shows the demographic and treatment data. All patients had Child-Turcotte-Pugh (CTP) A (score 5 in 17 patients and 6 in one patient), and no patient had portal vein tumor thrombosis. The median cumulative tumor diameter was 2.05 cm (range 1.0–4.4 cm). The dose was initially escalated to 52 Gy (13 Gy/fraction) without DLT. The protocol was amended for a further escalation to 60 Gy (15 Gy/fraction). The total number of patients analyzed in this study included additional patients enrolled in dose levels 1 and 3 while the amended protocols were being approved. Table 2 shows the dosimetric parameters from the radiotherapy planning. The median value for PTV was 79.9 cc (8.16 to 225.3 cc). The median normal liver volume was 1124 cc (801 to 1736 cc), and the median value of the mean dose to normal liver was 9.7 Gy (3.0 to 14.3 Gy).
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Abstract: Neovascular age-related macular degeneration is a leading cause of blindness in the developed world. Currently, the treatment of choice is intravitreal injections of anti-VEGF medications. These require frequent dosing, up to monthly, and impose a substantial burden on patients and the health economy. Ionizing radiation was proposed as a possible treatment for age-related macular degeneration due to its anti-inflammatory and anti-fibrotic properties. Stereotactic radiotherapy is an outpatient-based radiotherapy platform that provides stereotactic application of low energy X-ray to the retina in three highly collimated beams that cross the inferior sclera to overlap at the macula. A randomized, double-masked, sham-controlled trial of 230 patients (INTREPID) showed that a single dose of stereotactic radiotherapy significantly reduces the number of intravitreal anti-VEGF injections needed over 2 years. A larger random- ized controlled trial (STAR) is underway.
Abstract: Stereotactic body radiation therapy (SBRT) has emerged as a new technology in radiotherapy delivery, allowing for potentially curative treatment in many patients previously felt not to be candidates for radical surgical resection of stage I non-small-cell lung cancer (NSCLC). Several studies have demonstrated very high local control rates using SBRT, and more recent data have suggested overall survival may approach that of surgery in operable patients. However, SBRT is not without unique toxicities, and the balance of toxicity, and effect on patient-reported quality of life need to be considered with respect to oncologic outcomes. We therefore aim to review SBRT in the context of important patient-related factors, including quality of life in several domains (and in comparison to other therapies such as conventional radiation, surgery, or no treatment). We will also describe scenarios in which SBRT may be reasonably offered (i.e. elderly patients and those with severe COPD), and where it may need to be approached with some caution due to increased risks of toxicity (i.e. tumor location, patients with interstitial lung disease). In total, we hope to characterize the physical, emotional, and functional consequences of SBRT, in relation to other management strategies, in order to aid the clinician in deciding whether SBRT is the optimal treatment choice for each patient with early stage NSCLC. Keywords: non-small-cell lung cancer, early stage, stereotactic radiation, quality of life, toxicity
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