Using moderate or ultra-hypofractionation, which is also known as stereotactic body radiotherapy (SBRT) for treatment of localized prostate cancer patients has been increased. We present our ...preliminary results on the clinical utilization of MRI-guided adaptive radiotherapy (MRgRT) for prostate cancer patients with the workflow, dosimetric parameters, toxicities and prostate-specific antigen (PSA) response.
50 prostate cancer patients treated with ultra-hypofractionation were included in the study. Treatment was performed with intensity-modulated radiation therapy (step and shoot) technique and daily plan adaptation using MRgRT. The SBRT consisted of 36.25 Gy in 5 fractions with a 7.25 Gy fraction size. The time for workflow steps was documented. Patients were followed for the acute and late toxicities and PSA response.
The median follow-up for our cohort was 10 months (range between 3 and 29 months). The median age was 73.5 years (range between 50 and 84 years). MRgRT was well tolerated by all patients. Acute genitourinary (GU) toxicity rate of Grade 1 and Grade 2 was 28 and 36%, respectively. Only 6% of patients had acute Grade 1 gastrointestinal (GI) toxicity and there was no Grade ≥ 2 GI toxicity. To date, late Grade 1 GU toxicity was experienced by 24% of patients, 2% of patients experienced Grade 2 GU toxicity and 6% of patients reported Grade 2 GI toxicity. Due to the short follow-up, PSA nadir has not been reached yet in our cohort.
In conclusion, MRgRT represents a new method for delivering SBRT with markerless soft tissue visualization, online adaptive planning and real-time tracking. Our study suggests that ultra-hypofractionation has an acceptable acute and very low late toxicity profile.
MRgRT represents a new markerless method for delivering SBRT for localized prostate cancer providing online adaptive planning and real-time tracking and acute and late toxicity profile is acceptable.
We sought to determine the risk of leptomeningeal disease (LMD) in patients treated with stereotactic radiosurgery (SRS) targeting the postsurgical resection cavity of a brain metastasis, deferring ...whole-brain radiation therapy (WBRT) in all patients.
We retrospectively reviewed 175 brain metastasis resection cavities in 165 patients treated from 1998 to 2011 with postoperative SRS. The cumulative incidence rates, with death as a competing risk, of LMD, local failure (LF), and distant brain parenchymal failure (DF) were estimated. Variables associated with LMD were evaluated, including LF, DF, posterior fossa location, resection type (en-bloc vs piecemeal or unknown), and histology (lung, colon, breast, melanoma, gynecologic, other).
With a median follow-up of 12 months (range, 1-157 months), median overall survival was 17 months. Twenty-one of 165 patients (13%) developed LMD at a median of 5 months (range, 2-33 months) following SRS. The 1-year cumulative incidence rates, with death as a competing risk, were 10% (95% confidence interval CI, 6%-15%) for developing LF, 54% (95% CI, 46%-61%) for DF, and 11% (95% CI, 7%-17%) for LMD. On univariate analysis, only breast cancer histology (hazard ratio, 2.96) was associated with an increased risk of LMD. The 1-year cumulative incidence of LMD was 24% (95% CI, 9%-41%) for breast cancer compared to 9% (95% CI, 5%-14%) for non-breast histology (P=.004).
In patients treated with SRS targeting the postoperative cavity following resection, those with breast cancer histology were at higher risk of LMD. It is unknown whether the inclusion of whole-brain irradiation or novel strategies such as preresection SRS would improve this risk or if the rate of LMD is inherently higher with breast histology.
We aimed to present our initial clinical experience on the implementation of a stereotactic MR-guided online adaptive radiation therapy (SMART) for the treatment of liver metastases in ...oligometastatic disease.
Twenty-one patients (24 lesions) with liver metastasis treated with SMART were included in this retrospective study. Step-and-shoot intensity-modulated radiotherapy technique was used with daily plan adaptation. During delivery, real-time imaging was used by acquiring planar magnetic resonance images in sagittal plane for monitoring and gating. Acute and late toxicities were recorded both during treatment and follow-up visits.
The median follow-up time was 11.6 months (range, 2.2 to 24.6 months). The median delivered total dose was 50 Gy (range, 40 to 60 Gy); with a median fraction number of 5 (range, 3 to 8 fractions) and the median fraction dose was 10 Gy (range, 7.5 to 18 Gy). Ninety-three fractions (83.7%) among 111 fractions were re-optimized. No patients were lost to follow-up and all patients were alive except one at the time of analysis. All of the patients had either complete (80.9%) or partial (19.1%) response at irradiated sites. Estimated 1-year overall survival was 93.3%. Intrahepatic and extrahepatic progression-free survival was 89.7% and 73.5% at 1 year, respectively. There was no grade 3 or higher acute or late toxicities experienced during the treatment and follow-up course.
SMART represents a new, noninvasive and effective alternative to current ablative radiotherapy methods for treatment of liver metastases in oligometastatic disease with the advantages of better visualization of soft tissue, real-time tumor tracking and potentially reduced toxicity to organs at risk.
Abstract
BACKGROUND:
An alternative treatment option to whole-brain irradiation after surgical resection of brain metastases is resection cavity stereotactic radiosurgery (SRS).
OBJECTIVE:
To review ...the dynamics of cavity volume change after surgical resection with the goal of determining the optimal timing for cavity SRS.
METHODS:
Preresection tumor, postresection/pre-SRS cavity, and post-SRS cavity volumes were measured for 68 cavities in 63 patients treated with surgery and postresection cavity SRS. Percent differences between volumes were calculated and correlation analyses were performed to assess volume changes before and after SRS.
RESULTS:
For the majority of tumors, the postresection cavity volume was smaller than the preresection tumor volume by a median percent volume change of −29% (range, −82% to 1258%), with larger preresection tumors resulting in greater cavity shrinkage (P < .001). To determine the optimal timing for cavity SRS, we examined cavity volume dynamics by comparing the early postresection (postoperative days 0–3) and treatment planning magnetic resonance imaging scans (median time to magnetic resonance imaging, 20 days; range, 9-33 days) and found no association between the postresection day number and volume change (P = .75). The volume decrease resulting from tumor resection was offset by the addition of a 2-mm clinical target volume margin, which is our current technique.
CONCLUSION:
The greatest volume change occurs immediately after surgery (postoperative days 0–3) with no statistically significant volume change occurring up to 33 days after surgery for most patients. Therefore, there is no benefit of cavity shrinkage in waiting longer than the first 1 to 2 weeks to perform cavity SRS.
Access to cancer care is a problem that continues to plague refugees displaced from their home countries. The turbulent political crisis in Syria, which has led to millions of refugees seeking asylum ...in Turkey, merits further attention. We aimed to study the rate of utilization of radiation therapy among Syrian refugees with cancer living in Turkey in an attempt to identify the contributing factors predictive of non-compliance with prescribed RT.
In this retrospective review of 14 institutional databases, Syrian refugee patients in Turkey with a cancer diagnosis from January 2015 to December 2019 who were treated with RT were identified. The demographic data, treatment compliance rates, and toxicity outcomes in these patients were surveyed. Variable predictors of noncompliance such as age, sex, diagnosis, treatment length, and toxicity were studied. The association between these variables and patient noncompliance was determined.
We identified 10,537 patients who were diagnosed with cancer during the study period, of whom 1010 (9.6%) patients were treated with RT. Breast cancer (30%) and lung cancer (14%) were the most common diagnoses with up to 68% of patients diagnosed at an advanced stage (Stage III, IV). 20% of the patients were deemed noncompliant. Treatment with concurrent chemoradiotherapy (OR 1.61, 95% CI 1.06-2.46, p = 0.023) and living in a refugee camp (OR 3.62, 95% CI 2.43-5.19, p < 0.001) were associated with noncompliance. Age, sex and treatment length were not significantly associated with noncompliance.
Noncompliance with radiotherapy among Syrian refugees in Turkey remains an area of concern with a multitude of factors contributing to these alarming numbers. Further studies to better ascertain the finer nuances of this intricately complex problem and a global combination of efforts can pave the way to providing a solution.
Patients with tumors adjacent to the optic nerves and chiasm are frequently not candidates for single-fraction stereotactic radiosurgery (SRS) due to concern for radiation-induced optic neuropathy. ...However, these patients have been successfully treated with hypofractionated SRS over 2-5 days, though dose constraints have not yet been well defined. We reviewed the literature on optic tolerance to radiation and constructed a dose-response model for visual pathway tolerance to SRS delivered in 1-5 fractions. We analyzed optic nerve and chiasm dose-volume histogram (DVH) data from perioptic tumors, defined as those within 3 mm of the optic nerves or chiasm, treated with SRS from 2000-2013 at our institution. Tumors with subsequent local progression were excluded from the primary analysis of vision outcome. A total of 262 evaluable cases (26 with malignant and 236 with benign tumors) with visual field and clinical outcomes were analyzed. Median patient follow-up was 37 months (range: 2-142 months). The median number of fractions was 3 (1 fraction n = 47, 2 fraction n = 28, 3 fraction n = 111, 4 fraction n = 10, and 5 fraction n = 66); doses were converted to 3-fraction equivalent doses with the linear quadratic model using α/β = 2 Gy prior to modeling. Optic structure dose parameters analyzed included Dmin , Dmedian , Dmean , Dmax , V 30 Gy , V 25 Gy , V 20 Gy , V 15 Gy , V 10 Gy , V 5 Gy , D50% , D10% , D5% , D1% , D 1 cc , D 0.50 cc , D 0.25 cc , D 0.20 cc , D 0.10 cc , D 0.05 cc , D 0.03 cc . From the plan DVHs, a maximum-likelihood parameter fitting of the probit dose-response model was performed using DVH Evaluator software. The 68% CIs, corresponding to one standard deviation, were calculated using the profile likelihood method. Of the 262 analyzed, 2 (0.8%) patients experienced common terminology criteria for adverse events grade 4 vision loss in one eye, defined as vision of 20/200 or worse in the affected eye. One of these patients had received 2 previous courses of radiotherapy to the optic structures. Both cases were meningiomas treated with 25 Gy in 5 fractions, with a 3-fraction equivalent optic nerve Dmax of 19.2 and 22.2 Gy. Fitting these data to a probit dose-response model enabled risk estimates to be made for these previously unvalidated optic pathway constraints: the Dmax limits of 12 Gy in 1 fraction from QUANTEC, 19.5 Gy in 3 fractions from Timmerman 2008, and 25 Gy in 5 fractions from AAPM Task Group 101 all had less than 1% risk. In 262 patients with perioptic tumors treated with SRS, we found a risk of optic complications of less than 1%. These data support previously unvalidated estimates as safe guidelines, which may in fact underestimate the tolerance of the optic structures, particularly in patients without prior radiation. Further investigation would refine the estimated normal tissue complication probability for SRS near the optic apparatus.
Magnetic resonance-guided radiation therapy (MRgRT) has been incorporated into a growing number of clinical practices world-wide, however, there is limited data on patient experiences with MRgRT. The ...purpose of this study was to prospectively evaluate patient tolerance of MRgRT using patient reported outcome questionnaires (PRO-Q).
Ninety patients were enrolled in this prospective observational study and treated with MRgRT (MRIdian Linac System, ViewRay Inc. Oakwood Village, OH, United States) between September 2018 and September 2019. Breath-hold-gated dose delivery with audiovisual feedback was completed as needed. Patients completed an in-house developed PRO-Q after the first and last fraction of MRgRT.
The most commonly treated anatomic sites were the abdomen (47%) and pelvis (33%). Respiratory gating was utilized in 62% of the patients. Patients rated their experience as positive or at least tolerable with mean scores of 1.0-2.8. The most common complaint was the temperature in the room (61%) followed by paresthesias (57%). The degree of anxiety reported by 45% of the patients significantly decreased at the completion of treatment (mean score 1.54 vs. 1.36,
= 0.01). Forty-three percent of the patients reported some degree of disturbing noise which was improved considerably by use of music. All patients appreciated their active role during the treatment.
This evaluation of PROs indicates that MRgRT was well-tolerated by our patients. Patients' experience may further improve with adjustment of room temperature and noise reduction.
Objectives Improved soft-tissue visualization, afforded by magnetic resonance imaging integrated into a radiation therapy linear accelerator-based radiation delivery system (MR-linac) promises ...improved image-guidance. The availability of MR-imaging can facilitate on-table adaptive radiation planning and enable real-time intra-fraction imaging with beam gating without additional exposure to radiation. However, the novel use of magnetic resonance-guided radiation therapy (MRgRT) in the field of radiation oncology also potentially poses challenges for routine clinical implementation. Herein the early experience of a single institution, implementing the first MRgRT system in the country is reported. We aim to describe the workflow and to characterize the clinical utility and feasibility of routine use of an MR-linac system. Methods The ViewRay MRIdian MR-linac system consists of a split-magnet 0.35 T MR-imaging scanner with a double focused multi-leaf collimator (MLC) equipped 6MV linear accelerator. Unique to the system are the control console integrated on-table adaptive radiation therapy (oART) planning capabilities as well as automated beam gating based on real-time intra-fraction MR imaging. From the first day of clinical implementation, oART was performed according to physicians' discretion when medically indicated. All fractions were delivered under real-time imaging with soft tissue-based automated beam gating with individualized gating boundary settings. Patients actively assisted in breath-hold beam gating with the help of custom designed prismatic glasses allowing sight of a computer monitor mounted on the back wall just behind the MRI system bore. Patient demographics and treatment experience, indications for MRgRT including diagnosis and disease site, radiation dose prescribed and fractionation scheme, utilization of oART, respiratory gating settings, as well as duration of each treatment phase were analyzed. Results Between September 2018 and May 2019, 72 patients with 84 tumor sites were treated with MRgRT in 500 total fractions. Median patient age was 66 years (range: 28-83 years). Among 84 tumor sites, the most frequently treated regions were upper abdominal and pelvic (n = 36, 43% and n = 29, 34%, respectively). The most common diagnosis was prostate cancer, with 14 patients treated. In 69 patients (93.2%) oART was used at least once during a treatment course. Twenty-nine targets (43.1%) with significant breathing-related motion were treated in breath-hold with patient visual feedback. Median prescribed dose was 36.25 Gy (range: 24-70 Gy) in median five fractions (range: 3-28 fractions). A gating boundary of 3 mm around a gating region of interest (gROI) was most commonly used (range: 3-5 mm) with 95% of the gROI (range: 93-97%) required to be within the gating boundary for the beam to automatically engage. Mean total treatment time was 47 min (range: 21-125 min) and mean beam-on time was 16.7 min (range: 6-62 min). Conclusions MRgRT afforded by an MR-linac system has been successfully implemented into routine clinical use at our institution as the first system of its kind in Turkey. While the overall number of patients treated and fractions delivered is still limited, we have demonstrated the feasibility of both on-table adaptive radiation therapy as well as automated real-time beam gating on a daily basis in acceptable time schedules.
Lattice Radiotherapy (LRT) is a technique in which heterogeneous doses are delivered to the target so large tumors can have optimal doses of radiation without compromising healthy tissue sparing. To ...date, case reports and case series documented its application for bulky tumors mainly in the pelvic region. LRT not only provides dosimetric advantages but also promotes tumor control by triggering some radiobiological and immunological pathways. We report two cases of giant liver metastases for whom other treatment options were not suitable. We treated both patients with Magnetic Resonance Image-Guided Radiotherapy (MRgRT) with online adaptive LRT (OALRT) technique. Adaptive plans were generated before each fraction. Tumors were observed to have regressed interfractionally so the location and number of spheres were adapted to tumor size and daily anatomy of the surrounding organs at risk (OAR). Both patients had good treatment compliance without any Grade 3+ side effects. They are both under follow-up and report improvement. By reporting the first application of OALRT by using MRgRT in liver metastases, we show that MRgRT is a promising modality for LRT technique with better target and OAR visualization as well as online adaptive planning before each fraction according to the daily anatomy of the patient.
Lymphoid neoplasia derived from mucosa-associated lymphoid tissue (MALT; also abbreviated as MALToma) is most commonly seen in the stomach. Radiotherapy (RT) is indicated in early-stage disease as a ...standard of care. With the advent of RT techniques, large field irradiation was replaced by involved site and involved field approaches. Magnetic resonance imaging-guided online adaptive RT (MRgRT) has the advantage of better soft tissue visualization, adaptive planning before each fraction, and online tumor tracking during treatment; hence, it could be a safe and effective choice for gastric MALToma patients. Herein, we investigated the interfractional changes in target and the impact of MRgRT on daily dosimetry in a gastric MALToma case. A patient diagnosed with MALToma who failed to respond to antibacterial treatment was referred to our clinic for RT. He was found to be suitable for MRgRT. We treated the patient with MRgRT in 20 fractions to a total dose of 30 Gy. Reoptimized adaptive plans were generated before each fraction since the coverages of the original plan were inadequate in each fraction. The patient showed good compliance and tolerated the treatment well. To our knowledge, this is the first documented case of a gastric MALToma treated with MRgRT. MRgRT is safe and feasible for this patient group with improved target coverage using small planning target volume margins. Without online adaptive planning, the target coverages would be inadequate and we would risk surrounding tissues to get higher doses.