Hypofractionated Treatment Research Articles

Analysis of haemostasis biomarkers in patients with advanced stage lung cancer during hypofractionated radiotherapy treatment.

ObjectiveTo investigate the relationship between changes in inflammatory and coagulatory biomarkers before and after short palliative radiotherapy in patients with advanced stage lung cancer.MethodsThis prospective observational single-centre study enrolled patients with histologically- or cytologically-confirmed lung cancer who were eligible for palliative radiotherapy. Inflammatory and coagulatory biomarkers including complete blood count, D-dimer and fibrinogen levels were evaluated before and after short hypofractionated radiotherapy.ResultsSeventy-two patients with advanced stage lung carcinoma were enrolled in this study. Metastases were associated with an increase in white blood cells, neutrophils and mean platelet volume. Increased volume of the primary tumour had a borderline level of correlation with white blood cell and neutrophil counts. After radiotherapy, white blood cells, neutrophils, haemoglobin and lymphocyte counts were decreased. After radiotherapy, the change in fibrinogen and mean platelet volume were borderline significant.ConclusionThe levels of inflammatory and coagulatory biomarkers can be used to monitor treatment.

Under-reported dosimetry errors due to interplay effects during VMAT dose delivery in extreme hypofractionated stereotactic radiotherapy.

Radiotherapy of extracranial metastases changed from normofractioned 3D CRT to extreme hypofractionated stereotactic treatment using VMAT beam techniques. Random interaction between tumour motion and dynamically changing beam parameters might result in underdosage of the CTV even for an appropriately dimensioned ITV (interplay effect). This study presents a clinical scenario of extreme hypofractionated stereotactic treatment and analyses the impact of interplay effects on CTV dose coverage. For a thoracic/abdominal phantom with an integrated high-resolution detector array placed on a 4D motion platform, dual-arc treatment plans with homogenous target coverage were created using a common VMAT technique and delivered in a single fraction. CTV underdosage through interplay effects was investigated by comparing dose measurements with and without tumour motion during plan delivery. Our study agrees with previous works that pointed out insignificant interplay effects on target coverage for very regular tumour motion patterns like simple sinusoidal motion. However, we identified and illustrated scenarios that are likely to result in a clinically relevant CTV underdosage. For tumour motion with abnormal variability, target coverage quantified by the CTV area receiving more than 98% of the prescribed dose decreased to 78% compared to 100% at static dose measurement. This study is further proof of considerable influence of interplay effects on VMAT dose delivery in stereotactic radiotherapy. For selected conditions of an exemplary scenario, interplay effects and related motion-induced target underdosage primarily occurred in tumour motion pattern with increased motion variability and VMAT plan delivery using complex MLC dose modulation.

Derivation of mean dose tolerances for new fractionation schemes and treatment modalities

Avoiding toxicities in radiotherapy requires the knowledge of tolerable organ doses. For new, experimental fractionation schemes (e.g. hypofractionation) these are typically derived from traditional schedules using the biologically effective dose (BED) model. In this report we investigate the difficulties of establishing mean dose tolerances that arise since the mean BED depends on the entire spatial dose distribution, rather than on the dose level alone.A formula has been derived to establish mean physical dose constraints such that they are mean BED equivalent to a reference treatment scheme. This formula constitutes a modified BED equation where the influence of the spatial dose distribution is summarized in a single parameter, the dose shape factor. To quantify effects we analyzed 24 liver cancer patients for whom both proton and photon IMRT treatment plans were available.The results show that the standard BED equation—neglecting the spatial dose distribution—can overestimate mean dose tolerances for hypofractionated treatments by up to 20%. The shape difference between photon and proton dose distributions can cause 30–40% differences in mean physical dose for plans having identical mean BEDs. Converting hypofractionated, 5/15-fraction proton doses to mean BED equivalent photon doses in traditional 35-fraction regimens resulted in up to 10 Gy higher doses than applying the standard BED formula.The dose shape effect should be accounted for to avoid overestimation of mean dose tolerances, particularly when estimating constraints for hypofractionated regimens. Additionally, tolerances established for one treatment modality cannot necessarily be applied to other modalities with drastically different dose distributions, such as proton therapy. Last, protons may only allow marginal (5–10%) dose escalation if a fraction-size adjusted organ mean dose is constraining instead of a physical dose.

Cone-beam CT-based inter-fraction localization errors for tumors in the pelvic region

PurposeTo evaluate inter-fraction tumor localization errors (TE) in the RapidArc® treatment of pelvic cancers based on CBCT. Appropriate CTV-to PTV margins in a non-IGRT scenario have been proposed. MethodsData of 928 patients with prostate, gynecological, and rectum/anal canal cancers were retrospectively analyzed to determine systematic and random localization errors. Two protocols were used: daily online IGRT (d-IGRT) and weekly IGRT. The latter consisted in acquiring a CBCT for the first 3 fractions and subsequently once a week. TE for patients who underwent d-IGRT protocol were calculated using either all CBCTs or the first 3. ResultsThe systematic (and random) TE in the AP, LL, and SI direction were: for prostate bed 2.7(3.2), 2.3(2.8) and 1.9(2.2) mm; for prostate 4.2(3.1), 2.9(2.8) and 2.3(2.2) mm; for gynecological 3.0(3.6), 2.4(2.7) and 2.3(2.5) mm; for rectum 2.8(2.8), 2.4(2.8) and 2.3(2.5) mm; for anal canal 3.1(3.3), 2.1(2.5) and 2.2(2.7) mm. CTV-to-PTV margins determined from all CBCTs were 14 mm in the AP, 10 mm in the LL and 9–9.5 mm in the SI directions for the prostate and the gynecological groups and 9.5–10.5 mm in AP, 9 mm in LL and 8–10 mm in the SI direction for the prostate bed and the rectum/anal canal groups. If assessed on the basis of the first 3 CBCTs, the calculated CTV-to-PTV margins were slightly larger. Conclusionswithout IGRT, large CTV-to-PTV margins up to 15 mm are required to account for inter-fraction tumor localization errors. Daily IGRT should be used for all hypo-fractionated treatments to reduce margins and avoid increased toxicity to critical organs.

3D prompt gamma imaging for proton beam range verification

We tested the ability of a single Compton camera (CC) to produce 3-dimensional (3D) images of prompt gammas (PGs) emitted during the irradiation of a tissue-equivalent plastic phantom with proton pencil beams for clinical doses delivered at clinical dose rates. PG measurements were made with a small prototype CC placed at three different locations along the proton beam path. We evaluated the ability of the CC to produce images at each location for two clinical scenarios: (1) the delivery of a single 2 Gy pencil beam from a hypo-fractionated treatment (~9 × 108 protons), and (2) a single pencil beam from a standard treatment (~1 × 108 protons). Additionally, the data measured at each location were combined to simulate measurements with a larger scale, clinical CC and its ability to image shifts in the Bragg peak (BP) range for both clinical scenarios. With our prototype CC, the location of the distal end of the BP could be seen with the CC placed up to 4 cm proximal or distal to the BP distal falloff. Using the data from the simulated full scale clinical CC, 3D images of the PG emission were produced with the delivery of as few as 1 × 108 protons, and shifts in the proton beam range as small as 2 mm could be detected for delivery of a 2 Gy spot. From these results we conclude that 3D PG imaging for proton range verification under clinical beam delivery conditions is possible with a single CC.

An Evaluation of the ICON® Mask Fixation: Curing Characteristics of the Thermoplastic Fixation and Implications for Patient Workflow.

BackgroundThermoplastic mask immobilization is used to perform hypo-fractionated treatments with the Gamma Knife ICON®.Materials and methodsWe evaluated the curing characteristics of the ICON® Nanor mask using force sensing resistors coupled with a data logging tool designed by us.ResultsFor patients being treated with masks made the same day as the treatment, often in the same sitting with no removal and replacement of the patient from the treatment cradle, based on the curves 80% of the force of fixation is reached at 30 minutes.ConclusionsAllowing for curing over 10-15 minutes and the subsequent localizing and delivery Cone beam CT (CBCT)s as well as the plan evaluation this is a reasonable time to start of therapy. For more exacting targets that are still requiring hypo-fractionation a cure period of 15 hours or greater will ensure that maximum rigidity of fixation is achieved.

PET/CT and Hypo-Fractionated Radiotherapy of Patients with Head and Neck Cancer

Positron emission tomography/Computer tomography (PET/CT) is a multimodality imaging diagnostic technique that analyzes the uptake and retention of different radiopharmaceuticals by cells providing metabolic information on biochemical processes. PET/CT has been used for radiotherapy planning, providing useful information to the Radio-oncologist about the localization, size and metabolic activity of tumor lesions. In this paper, we show advantages of the 18F-FDG PET/CT respect to simple CT imaging for target volume delineation in patients with diagnosis of Squamous Head and Neck Carcinoma that has been scheduled to undergo a hypofractionated radiotherapy treatment. On ten studied patients, the target volume defined from PET/CT images was less extensive than those defined from simple CT images. In six patients the target volume was significantly less extensive and in two of them a new lymph node disease was reported, re-staging and corresponding target volume was also delineated with less extensive margins from PET/CT images. A greater accuracy in delineating the volumes and improving the distribution of doses in the planning of the radiant treatment in these patients was possible, allowing a high precision in the delivery of the prescribed dose to the target volume diminishing the maximum dose to the adjacent healthy tissues. In conclusion we show that the use of 18F-FDG PET/CT was superior than the simple CT as the primary modality of imaging for hypofractioned radiotherapy treatment planning in patients with Squamous Head and Neck Carcinoma.

32. Comparative study of planimetry for patients with 3 brain metastases treated with Cyberknife: Treatment of 3 lesions separately versus 3 simultaneous lesions

Introduction The aim of this study is to compare the irradiation of three brain lesions treated as consecutive and mono-fractionated to the Cyberknife with simultaneous treatment including the 3 lesions. Methods We study in this work 12 patients with 3 brain lesions who each have been processed at the dose of 20 Gy in 1 fraction. These small tumors (mean 8 cc: min 0.4 cc, max 3.5 cc) were distant from each other. We realized after the fact a planimetry including the three lesions for a simultaneous treatment. To do this, we create a PTV Global volume on which we apply our dose constraints. We then compare the coverage, dosimetric indices (conformity index, homogeneity index, gradient), the processing time and doses to the brain. This study will allow us on the one hand, to assess the feasibility of the treatment, and on the other hand to propose the planimetry to the doctor according to the patient’s case. To improve and secure our study, each patient received a double dosimetry performed by two different operators through the Multiplan planning console, which is dedicated to the Cyberknife. Results The duration of the sessions for the 3 lesions treated simultaneously is acceptable for the patient with values between 45 min and 63 min (mean 55 min), which corresponds to an average increase of 71% (7–127%). This processing time is still acceptable and the simultaneous treatment is time saving for the machine since we have a discrepancy between these two treatment schemes, with an average gain of 83% (59–147%). We evaluated doses received by the healthy brain in the two schemes: V12 Gy, V10 Gy, V8 Gy, V5 Gy. Conclusions In the context of the increase of small brain metastases treatment, the current trend is clearly towards hypo-fractionated treatment of the multi-localizations compared to the treatment of the whole of the brain. The comparison of the two treatment schemes allows us to propose in the future the solution of simultaneous treatment.

Conventional fractionation should not be the standard of care for T2 glottic cancer

BackgroundThe aim of this study was to report outcomes and late toxicity following hypofractionated accelerated radiotherapy for T2 glottic cancers. We highlight the importance of hypofractionated treatments with shorter overall treatment times, in improving outcomes for T2 glottic cancers. We also compare the biologically effective dose of hypofractionated regimes, with conventional fractionation.MethodsOne hundred twelve patients with T2 glottic cancer were treated between January 1999 and December 2005. All patients were prescribed a hypofractionated accelerated radiotherapy dose of 52.5 Gray in 3.28 Gray per fraction, delivered over 22 days. Radiobiological calculations were used to assess the relationship of fraction size and overall treatment time on local control outcomes and late toxicity.ResultsThe 5-year overall survival was 67%, the 5-year local control was 82%, and the 5-year disease-specific survival was 90%. The respective 5-year local control for T2a and T2b disease was 88.8 and 70.8% (p = 0.032). Severe late toxicity occurred in two patients (1.8%). Radiobiological calculations showed an increase in local control of nearly 12%, with a 10 Gray increase in biologically effective dose.ConclusionThis study has demonstrated that accelerated hypofractionated regimes have improved local control and similar late toxicity compared with conventional fractionation schedules. This supports the use of hypofractionated regimes as the standard of care for early glottic laryngeal cancers.

Effect of Hypofractionation on Prostate Cancer Radiotherapy

Context: Prior research over the past few decades has shown that the hypofractionated external beam radiation therapy could be a valuable method with an outstanding potential to treat the prostate cancer. The alpha-beta ratio (α/β) is an indication of the fractionation sensitivity of a particular cell type. Values of α/β ≥ 10 Gy are responsible for early-responding normal tissues and most tumors, while values of α/β < 5 Gy are for late-responding normal tissues. The α/β ratio could be raised by either a local tumor control increase or a decrease of normal tissue late effects through the application of an unconventional fractionation schedules. Evidence Acquisition: This review article aimed to investigation the details of radiobiological and clinical trials which are reported to highlight the characteristics of hypofractionation for the prostate cancer treatment based on the investigation of clinical results from hypofractionated treatments. Results: With the sufficient radiobiological and physiological research studies, it may be claimed that if α/β value for prostate cancer is less than the adjacent surrounding organs at risk and by applying fewer and larger fractions; a better therapeutic ratio can be achieved for the patient. Conclusions: Radiobiological modeling can play a major role in the design of new protocols. Also, one should be aware that in modeling the hypofractionated treatment, normal tissue iso-effects are significantly important and some assumptions needed to be made regarding α/β values for the critical normal tissue complication endpoint.

Automated prediction of dosimetric eligibility for hypofractionated prostate radiotherapy.

Clinical implementation of hypofractionated prostate radiotherapy (PROFIT trial, NCT003046759) represents an opportunity to significantly reduce the burden of treatment on the patient and clinic. However, efficacy was only demonstrated among the patient demographic who could meet the trial dose constraints and so it is necessary to emulate this triage step in clinical practice. The purpose of this study was to build a convenient tool to address the challenge of determining patient eligibility for hypofractionated treatment within the clinic. The tool was implemented within the EclipseTM treatment planning system using the scripting environment. Prior to planning a new case, the script computes and displays in a plot the fractional overlap of rectal and bladder wall with the planning target volume. Radial decision boundaries separate the plot into three zones and the new case is then classified as “feasible”, “uncertain”, or “not feasible”. The radial decision boundaries were derived from a retrospective analysis of the overlap values and dosimetric eligibility of 150 patients with intermediate risk prostate cancer. Two‐fold cross validation with repetitions demonstrated an average prediction accuracy of over 90%. The tool has been integrated into our clinical planning workflow to enable early identification of the need for planning consults and rapid a‐priori determination of dosimetric eligibility for hypofractionated radiotherapy. The tool can be readily adopted by other centres since the underlying metrics can be evaluated without scripting if desired.

An Integrated Real-time Monitored Liver SBRT Using Abdominal Compression

Literature reports suggest that cranial-caudal (CC) motion of abdominal tumors due to respiration can be significantly reduced using a pneumatic compression belt. Here, we describe our initial experience of liver SBRT using an integrated real-time monitored treatment using triggered kV images and a pneumatic compression belt. All patients had 3 fiducial markers implanted near the liver tumor prior to simulation. 10 initial patients were eligible abdominal compression with a selected cut off that CC fiducial motion is > 5 mm without compression and ≤5 mm with compression, measured fluoroscopically. The pressure reading of the air bag and the belt length were recorded for set-up during 3 hypo-fractionated treatments. Polymer/Carbon fiducials were contoured as high-resolution structures in planning CT. An additional structure “fid+5mm” was created around each fiducial with a 5 mm margin. Margin expansion from CTV to PTV was 5 mm. Orthogonal kV images and CBCT images were acquired for patient alignments and pre-treatment verification. 9 patients had a 2-arc VMAT plan and 1 had 7 field IMRT treated with 10X-FFF mode with triggered imaging for real-time verification. Variation in target alignment due to residual respiratory motion and set-up errors was assessed by measuring fiducial shifts between the Planning and Pre-treatment orthogonal kV images. 87 pairs of fiducial positions were compared over entire treatment course. 64 fiducial pairs (73%) had deviation < 3 mm and 81 pairs (93%) had deviation < 5 mm. In 6 pairs (7%) the deviation was between 6 and 8 mm. A median 34 (range 34-79) trigger images were acquired during each delivery session to ensure fiducials were within “fid+5mm” contour. In 54% of sessions, beam delivered without interruption. Beam start-to-finish time was 122-223 sec for 9 patients with 2-arc VMAT, and 530 sec for 1 patient with 7 field IMRT. In 21% of sessions, treatment beam was put ‘on hold’ 1-3 times as the fiducials moved out of the “fid+5mm” contour due to abnormal breathing under compression. Treatment was continued after the fiducials returned to their original position. This “on hold” beam interruption added extra 53 sec (median, range 46-288 sec) to each delivery session. Re-imaging and re-adjustment of patient position was required in the rest 25% of sessions, and it took extra 220 sec (median, range 156-1513 sec). In a selected patient cohort, liver SBRT can be delivered efficiently using a pneumatic compression belt and verified with real-time monitored treatment delivery using triggered kV images.

Improving CT quality with optimized image parameters for radiation treatment planning and delivery guidance

Abstract Background and purpose CT scan protocols are often created with imaging parameters set to minimize imaging dose with acceptable image quality for diagnostic purpose. This study aimed to optimize CT imaging parameters to help accurately delineate structures for radiation therapy planning and delivery guidance. Materials and methods Imaging parameters were optimized with CT data acquired for a phantom to create image quality enhancement (IQE) protocols, which were subsequently used to scan a prostate and a pancreatic cancer patient who underwent image-guided radiotherapy (IGRT). The patient images were compared with those scanned with standard clinical protocols, the quality of these images was assessed with various methods (survey, inter- and intra-observer variations, and dice coefficient analysis) for the two patient cases. Results An effective tube current–time product of ∼1000 mAs was found to be a reasonable choice to balance CT quality and CT dose. With increased dose and penetration taken into account, 100 and 120 kV tube voltages were found appropriate for the IQE protocols. The inter- and intra-observer variations for the IQE data were smaller than those with the standard protocols. Dice coefficient analysis indicated that the IQE protocols lead to improved dice coefficient by as much as 8 percentage points for the two cases studied. Conclusion CT image quality can be improved with the IQE protocols created in this study, to provide better soft tissue contrast, which would be beneficial for use in radiation therapy, e.g., for planning data acquisition or for IGRT for hypo-fractionated treatments.

The Dosimetric Effect of Prostate Motion in Flattening Filter Free VMAT Treatments Using Extreme Hypofractionation

To evaluate the performance of two treatment planning systems (TPS), using radiotherapy beams both with and without flattening filter, for extreme hypo-fractionated prostate cancer treatment. The TPSs were evaluated regarding plan quality and robustness with respect to prostate motion. With hypofractionation, the treatment time per fraction is increased, making prostate motion more significant. Flattening filter free treatments can decrease the treatment time due to the higher dose rate, and therefore reduce the effect of prostate motion. Prostate cancer patients treated with extreme hypofractionation (7x6.1 Gy=42.7 Gy) in the experimental arm of the randomized Scandinavian HYPO-RT-PC trial were used in this study. The TPSs used were Varian Eclipse (Varian Medical Systems) and RayStation (RaySearch Laboratories). The treatment plan comparison was made using the Pareto front method. Several VMAT plans were optimized with varying importance assigned to rectal sparing and PTV coverage objectives. The rectal volume receiving more than 90%, (Rectum, V90%), of the prescribed dose was plotted as a function of the PTV under dosage, (PTV, V95%). Two different beam qualities were used on each TPS, 10MV with flattening filter (FF) and 10MV flattening filter free (FFF). All plans were made for a Varian TrueBeam accelerator. The Pareto optimal plans, where one objective cannot be improved without deteriorating the other, formed a front for each TPS and beam quality. Three plans for each Pareto front were selected for measurement from three different regions in the fronts. These were defined as follows: PTV more important than Rectum (PTV>>Rect), Rectum more important than PTV (Rect>>PTV) and the knee of the Pareto front. The latter is the point where the target coverage starts to drastically decrease without significant improvement in rectum dose. The measurements were performed using the Delta4 Phantom+ (ScandiDos) and motion was simulated using the HexaMotion device with realistic motion patterns. The measurements were evaluated with gamma analysis using the local clinical protocol at our clinic (90% pass rate at 3%/2mm). The Pareto front plan comparison showed very small differences between the two TPSs and beam qualities. Eclipse had slightly better target coverage in the PTV>>Rect region but RayStation had lower rectum doses in the Rect>>PTV region. All plans fulfilled the dose-volume constraints of the trial protocol. However, all fronts showed that the rectum dose could be decreased even more without losing target coverage. The static measurements showed 100% pass rate for all plans. For the in-motion measurements, the FF plans had a pass rate below the clinically acceptable 90% pass rate while the FFF plans were above 90%. The beam-on time was decreased from 2.5 min to 1 min. Both TPSs delivered plans with good quality for both FF and FFF beams. The FFF plans proved to be clinically acceptable even with prostate motion for both TPSs.

Daily Positioning Variations in Image Guided Radiation Therapy of Pancreatic Cancer

Margin reduction and hypo-fractionated treatment of pancreatic cancer is increasing in interest and practice in radiation oncology, but pancreatic motion has the potential to limit clinical efficacy. This study details the magnitude of observed positional variations of pancreatic tumors treated with radiation therapy utilizing the results of daily image guided radiation therapy (IGRT). Daily IGRT shifts based on cone-beam CT (CBCT) and mega-voltage CT (MVCT) were recorded and evaluated in order to estimate positioning variations of pancreatic target volumes. A total of 72 patients and 1159 3D-images captured immediately prior to daily conventionally fractionated RT were considered. Overall positioning variations, inter-patient variations, and correlations between position variations and patient-specific factors including PTV volume, tumor location (head/body/tail of pancreas), and central or lateral positioning of the PTV were estimated. Statistical analysis of the positioning variations included Kolmogorov-Smirnov (KS) testing for normality of distributions. Estimation of appropriate margins was carried out based on M=2.5Σ+0.7σ assuming the measured inter-fraction shifts are representative of intra-fraction motion, and present a conservative estimate of spatial expansions to ensure coverage of the CTV. Mean and standard deviation of IGRT shifts for all patients was 0.2±5.2 mm in lateral directions, -0.3±4.3 mm in vertical directions, and -0.7±5.5 mm in longitudinal directions. The systematic variation (the standard deviation of inter-patient average shifts) was 2.6 mm, 2.6 mm, and 3.0 mm in lateral, vertical, and longitudinal directions. The random variation (the average of inter-patient standard deviations) was 3.9 mm, 3.0 mm, and 4.1 mm lateral, vertical, and longitudinal directions. Combined, these results suggest uniform margins about the CTV up to 10.4 mm are sufficient to account for observed positioning variations during IGRT. For each patient, KS testing implies the patient-specific shifts were representative of Gaussian distributions for 70/72 patients and 2/216 patient-specific directional distributions. The patient-specific distributions were not correlated with PTV volume, central or lateral location of the PTV, or whether the tumor was in the pancreatic head, tail, or body. Pancreas is a mobile organ with potential for large motion; our results suggest this motion is normally distributed and well-represented by Gaussian distributions. If intra- and inter- fraction motion are similar, which is plausible if pancreas motion is due to breathing and gastrointestinal motion, our data suggest margins of 10.4 mm will account for these spatial variations. These margins will surely overlap with surrounding bowel, duodenum, and/or stomach and imply dose escalation of margin-based PTVs may not be feasible.

Short-Term Follow-Up Mammography in Breast Conservation Therapy Likely Leads to Unnecessary Downstream Workup: A Longitudinal Study

Toanalyze the effect of post-radiation therapy (XRT) mammographic timing and radiation technique in relation to additional downstream workup for 569 breast conservation therapy patients treated with adjuvant XRT after their initial surveillance mammogram (MMG). From January 2011 to December 2014, 569 breast cancer patients treated with breast conservation surgery and adjuvant XRT with a follow-up MMG were reviewed. Patients were stratified by the time interval until their first post-XRT MMG, and by XRT technique-whole breast (472), accelerated partial breast (96), conventional fractionation (373), hypofractionation (94), surgical cavity boosts (407), or no boost (66). The primary endpoint was further imaging after the initial MMG. Additional workup for those receiving an MMG within 3months of completing XRT was 51% (73 of 143), compared with 40% (84 of 210) with MMG between 3 and 6months and 34.5% (75 of 216) with MMG after 6months (P=.04). Radiation boost to the postoperative bed was associated with further downstream imaging, whereas accelerated partial-breast irradiation and hypofractionated treatment were not. Breast conservation therapy patients who underwent screening MMG before 6months after completion of XRT were more likely to undergo downstream workup, including additional biopsies. Accelerated and hypofractionated radiation techniques were not associated with supplementary workup. Further study is needed to assess appropriate selection of high-risk patients and possible negative implications of earlier post-XRT screening MMG.

Effect of intra-fraction motion on the accumulated dose for free-breathing MR-guided stereotactic body radiation therapy of renal-cell carcinoma

Stereotactic body radiation therapy (SBRT) has shown great promise in increasing local control rates for renal-cell carcinoma (RCC). Characterized by steep dose gradients and high fraction doses, these hypo-fractionated treatments are, however, prone to dosimetric errors as a result of variations in intra-fraction respiratory-induced motion, such as drifts and amplitude alterations. This may lead to significant variations in the deposited dose. This study aims to develop a method for calculating the accumulated dose for MRI-guided SBRT of RCC in the presence of intra-fraction respiratory variations and determine the effect of such variations on the deposited dose. For this, RCC SBRT treatments were simulated while the underlying anatomy was moving, based on motion information from three motion models with increasing complexity: (1) STATIC, in which static anatomy was assumed, (2) AVG-RESP, in which 4D-MRI phase-volumes were time-weighted, and (3) PCA, a method that generates 3D volumes with sufficient spatio-temporal resolution to capture respiration and intra-fraction variations. Five RCC patients and two volunteers were included and treatments delivery was simulated, using motion derived from subject-specific MR imaging. Motion was most accurately estimated using the PCA method with root-mean-squared errors of 2.7, 2.4, 1.0 mm for STATIC, AVG-RESP and PCA, respectively. The heterogeneous patient group demonstrated relatively large dosimetric differences between the STATIC and AVG-RESP, and the PCA reconstructed dose maps, with hotspots up to of the D99 and an underdosed GTV in three out of the five patients. This shows the potential importance of including intra-fraction motion variations in dose calculations.

Can a commercial gel dosimetry system be used to verify stereotactic spinal radiotherapy treatment dose distributions?

This study investigated the use of the TruView xylenol-orange-based gel and VISTA optical CT scanner (both by Modus Medical Inc, London, Canada), for use in verifying the accuracy of planned dose distributions for hypo-fractionated (stereotactic) vertebral treatments. Gel measurements were carried out using three stereotactic vertebral treatments and compared with planned doses calculated using the Eclipse treatment planning system (Varian Medical Systems, Palo Alto, USA) as well as with film measurements made using Gafchromic EBT3 film (Ashland Inc, Covington, USA), to investigate the accuracy of the gel system. The gel was calibrated with reference to a moderate-dose gradient region in one of the gel samples. Generally, the gel measurements were able to approximate the close agreement between the doses calculated by the treatment planning system and the doses measured using film (which agreed with each other within 2%), despite lower resolution and bit depth. Poorer agreement was observed when the dose delivered to the gel exceeded the range of doses delivered in the calibration region. This commercial gel dosimetry system may be used to verify hypo-fractionated treatments of vertebral targets, although separate gel calibration measurements are recommended.

Predicting late fecal incontinence risk after RT for prostate cancer: External independent validation.

116 Background: To validating a predictive model for late fecal incontinence (FI) on a recent population (pop) of prostate cancer patients (pts) treated with radical radiotherapy. NTCP model was derived from literature. Methods: Pop included 267 pts treated with IMRT in 2010-2014. Prescribed dose was between 68 and 80 Gy with conventional and hypo-fractionated (HF, from 2.2 to 2.8 Gy) treatment. Rectal toxicity was scored using the LENT/SOMA. Follow-up (FU) was considered up to 2 years. We chose to validate a model for prediction of chronic FI through multiple measures during FU. Mean FI was defined as the average score during the FU period after RT (Mean incontinence &gt; 1). Literature based multivariate model included: mean rectal dose (Dmean), previous diseases of colon (COLO) and previous abdominal surgery (SURG). Dose distributions were corrected EQD in 2 Gy fractions. Results: 186 pts were available. Mean grade &gt; 1 FI was scored in 18 patients (〜10%). Univariate logistic analysis confirmed the risk factors reported in literature. Similar Odds Ratios (OR) were found for Dmean (1.04vs1.05) and SURG (1.90vs1.50). COLO was not a risk factor for this pop. As consequence, NTCP models including Dmean and Dmean+SURG were evaluated through calibration plot. The models showed a clear trend (increasing observed toxicity rates with predicted risk), but the observed toxicity rates were underestimated (slope〜3, R2〜0.7). Including HF (OR = 2.20, 8.6% vs 17.6%) as a variable into the previous model the calibrations improved significantly (slope〜1, R2〜0.9). Conclusions: The study confirms formerly published results on effect of abdominal surgery and dose to large rectal volumes as potential risk factors for late FI. The overfitting in calibrations could be due to an effect of HF, not included in previous models developed on normofractionated treatments. This effect goes beyond the applied standard correction using LQ model for late effects and also beyond the time recovery correction (slope〜2, R^2〜0.8). Probably we should found a more suitable alpha/beta value for the longitudinal definition (toxicity starting in acute phase and persisting during follow-up) instead of using the assumption settled on incidence of late peak events.

Stereotactic spine radiosurgery: Review of safety and efficacy with respect to dose and fractionation.

Background:Stereotactic body radiotherapy (SBRT) is an emerging treatment option for spinal metastases with demonstrated efficacy in the upfront, postoperative, and re-treatment settings, as well as for tumor histologies considered radioresistant. Uncertainty exists regarding the optimal dose and fractionation schedule, with single and multifraction regimens commonly utilized.Methods:A literature search of the PubMed and Medline databases was conducted to identify papers specific to spine SBRT and the effect of varying dose/fractionation regimens on outcomes. Bibliographies of relevant papers were searched for further references, and international spine SBRT experts were consulted.Results:Local control rates generally exceed 80% at 1 year, while high rates of pain control have been attained. There is insufficient evidence to suggest superiority of either single or multiple fraction regimens with respect to local control and pain control. Low rates of toxicity have been reported, assuming strict dose constraints are respected. Radiation myelopathy may be the most morbid toxicity, although the rates are low. The risk of vertebral compression fracture appears to be associated with higher doses per fraction such as those used in single-fraction regimens. The Spinal Instability Neoplastic Score should be considered when evaluating patients for spine SBRT, and prophylactic stabilisation may be warranted. Pain flare is a relatively common toxicity which may be mediated with prophylactic dexamethasone. Because of the treatment complexity and potentially serious toxicities, strict quality assurance should occur at the organizational, planning, dosimetric, and treatment delivery levels.Conclusion:Both single and multifraction regimens are safe and efficacious in spine SBRT for spinal metastases. There may be advantages to hypofractionated treatment over single-fraction regimens with respect to toxicity. Ongoing investigation is underway to define optimal dose and fractionation schedules.