Abstract Background A randomised phase-III trial compared external beam radiotherapy (EBRT) alone with EBRT combined with high-dose-rate brachytherapy boost (HDR-BTb) in localised prostate ...adenocarcinoma. Methods From December 1997 to August 2005, 218 patients were assigned to EBRT alone ( n = 108) or EBRT followed by a temporary high-dose-rate implant ( n = 110). Patients were stratified according to tumour stage, PSA, Gleason score and androgen deprivation therapy (ADT). Biochemical/clinical relapse-free survival (RFS) was the primary endpoint. Secondary endpoints were overall survival (OS), urinary and bowel toxicity. Results RFS was significantly higher in patients treated with EBRT + HDR-BTb (log rank p = 0.04). In multivariate analysis treatment arm, risk category and ADT were significant covariates for risk of relapse. Differences in OS were not significant. Incidence of severe late urinary and bowel morbidity was similar. Conclusions EBRT + HDR-BTb resulted in a significant improvement in RFS compared to EBRT alone with a 31% reduction in the risk of recurrence ( p = 0.01) and similar incidence of severe late urinary and rectal morbidity.
•12 year results confirm HDR boost improves prostate cancer relapse free survival.•No difference in overall survival is seen.•No excess toxicity is seen in the HDR boost arm.
A randomised phase-III ...trial compared external beam radiotherapy (EBRT) alone with EBRT combined with high-dose-rate brachytherapy boost (HDR-BTb) in localised prostate adenocarcinoma. Previous analysis, at median follow up of 85 months, demonstrated improved relapse free survival (RFS) with EBRT + HDR-BTb. This data has now been updated with a median follow up of 131 months.
From December 1997 to August 2005, patients were assigned either to EBRT alone delivering 55 Gy in 20 fractions over 4 weeks or EBRT followed by a temporary high-dose-rate implant delivering 2 × 8·5 Gy over 24 h. The primary endpoint was RFS defined by a PSA rise ≥2.0 µg/l above nadir, clinical progression or death. Actuarial survival rates and Hazard Ratios (HRs) were calculated using the Kaplan–Meier method and Cox’s Proportional Hazard Model, respectively. Secondary endpoints were overall survival (OS), urinary and bowel toxicity.
One hundred and six patients received EBRT alone and 110 EBRT + HDR-BTb. Median time to relapse was 137 months in the HDR-BTb arm compared to 82 months for EBRT alone (p = 0·01). A 27% risk of recurrence with EBRT alone was observed (p = 0·001), resulting in a 21% improvement in RFS at 12 years with EBRT + HDR-BTb. In multivariate analysis treatment arm, risk category and no androgen deprivation therapy were significant covariates for risk of relapse. Differences in overall survival were not significant.
At 12 years there remains a significant improvement in RFS after EBRT + HDR-BTb; both treatments were equitoxic for severe late urinary and bowel events and urethral strictures.
To correlate computed tomographic (CT) texture in non-small cell lung cancer (NSCLC) with histopathologic markers for angiogenesis and hypoxia.
The study was institutional review board approved, and ...informed consent was obtained. Fourteen patients with NSCLC underwent CT prior to intravenous administration of pimonidazole (0.5 g/m(2)), a marker of hypoxia, 24 hours before surgery. Texture was assessed for unenhanced and contrast material-enhanced CT images by using a software algorithm that selectively filters and extracts texture at different anatomic scales (1.0 fine detail to 2.5 coarse features), with quantification of the standard deviation (SD) of all pixel values and the mean value of positive pixels (MPP) and uniformity of distribution of positive gray-level pixel values (UPP). After surgery, matched tumor sections were stained for angiogenesis (CD34 expression) and for markers of hypoxia (glucose transporter protein 1 Glut-1 and pimonidazole). The percentage and average intensity of the tumor stained were assessed. A linear mixed-effects model was used to assess the correlations between CT texture and staining intensity.
SD and MPP quantified from medium to coarse texture on contrast-enhanced CT images showed significant associations with the average intensity of tumor staining with pimonidazole (for SD: filter value, 2.5; slope = 0.003; P = .0003). UPP (medium to coarse texture) on unenhanced CT images showed a significant inverse association with tumor Glut-1 expression (filter value, 2.5; slope = -115.13; P = .0008). MPP quantified from medium to coarse texture on both unenhanced and contrast-enhanced CT images showed significant inverse associations with tumor CD34 expression (unenhanced CT: filter value, 1.8; slope = -0.0008; P = .003; contrast-enhanced CT: filter value, 1.8; slope = -0.0006; P = .004).
Texture parameters derived from CT images of NSCLC have the potential to act as imaging correlates for tumor hypoxia and angiogenesis.
http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12112428/-/DC1.
Quality assurance remains a neglected component of many trials, particularly for technical interventions, such as surgery and radiotherapy, for which quality of treatment is an important component in ...defining outcomes. We aimed to evaluate evidence for the processes used in radiotherapy quality assurance of clinical trials. A systematic review was undertaken focusing on use of a pre-trial outlining benchmark case and subsequent on-trial individual case reviews of outlining for recruited patients. These pre-trial and on-trial checks are used to ensure consistency and standardisation of treatment for each patient recruited to the trial by confirming protocol compliance. Non-adherence to the trial protocol has been shown to have a negative effect on trial outcomes. 29 studies published between January, 2000, and December, 2022, were identified that reported on either outlining benchmark case results or outlining individual case review results, or both. The trials identified varied in their use of radiotherapy quality assurance practices and reporting of outcomes was inconsistent. Deviations from trial protocols were frequent, particularly regarding outlining. Studies correlating benchmark case results with on-trial individual case reviews provided mixed results, meaning firm conclusions could not be drawn regarding the influence of the pre-trial benchmark case on subsequent on-trial performance. The optimal radiotherapy quality assurance processes were unclear, and there was little evidence available. Improved reporting of outcomes from radiotherapy quality assurance programmes is needed to develop an evidence base for the optimal approach to radiotherapy quality assurance in trials.
•This study reported treatment outcomes for prostate cancer patients receiving ultra-hypofractionated radiotherapy using high dose-rate brachytherapy (HDR BT) and stereotactic ablative radiotherapy ...(SABR).•26 Gy/2 fractions HDR BT provided equivalent biochemical disease control with lower toxicity compared to 36.25 Gy/5 fractions SABR.•Both 2-fraction HBR BT and 5-fraction SABR achieved better biochemical disease control than single dose 19 Gy HDR BT.
To compare the biochemical control rates (BCRs), late gastrointestinal (GI) and genitourinary (GU) toxicities in patients with low- and intermediate risk prostate cancer (PCa) treated with high-dose-rate brachytherapy (HDR BT) of 19 Gy/1 fraction, 26 Gy/2 fractions, or stereotactic ablative radiotherapy (SABR) of 36.25 Gy/5 fractions.
Between August 2008 and December 2017, patients with low- and intermediate risk PCa who received single dose or 2-fraction HDR BT, or 5-fraction SABR at a single institution were included. BCR for the whole population and the individual treatment groups were calculated using the Phoenix definition. Post treatment GI and GU toxicities were evaluated according to the CTCAE v4.0 guidelines.
185 patients with low- and intermediate risk PCa were included in this study with a median follow up of 60.5 months. BCRs at 3 and 5 years were 95% and 85% for all patients. The 5-year BCRs were 69%, 95% and 92% for the 19 Gy/1 fraction, 26 Gy/2 fractions and 36.25 Gy/5 fractions groups respectively. The cumulative 5-year incidence rates of ≥grade 2 GI events in the 19 Gy/1fr, 26 Gy/2fr and 36.25 Gy/5fr groups were 0%, 2% and 4%, respectively. Incidence rates in those treated in the 5-fraction SABR arm were significantly higher (p < 0.05) than those treated in both HDR BT arms where no statistically significant difference between the two HDR BT groups was seen (p = 0.15). The cumulative 5-year incidence rates of ≥grade 2 GU events in the 19 Gy/1fr, 26 Gy/2fr and 36.25 Gy/5fr groups were 30%, 5% and 6%, respectively. No statistically significant difference was found between the 26 Gy/2fr and 36.25 Gy/5fr (p = 0.37) treatment arms but the incidence rate in the 26 Gy/2fr were significantly lower than those seen after 19 Gy/1fr (p < 0.05).
26 Gy/2 fractions HDR BT provided equivalent BCR with lower toxicity compared to 36.25 Gy/5 fractions SABR. Both 2-fraction HBR BT and 5-fraction SABR achieved better BCRs than single dose 19 Gy HDR BT. The two-fraction HDR BT schedule should be considered as an important comparator in future clinical trials.
Magnetic resonance‐guided radiation therapy: A review Chin, Stephen; Eccles, Cynthia L; McWilliam, Alan ...
Journal of medical imaging and radiation oncology,
February 2020, Letnik:
64, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Summary
Magnetic resonance‐guided radiation therapy (MRgRT) is a promising approach to improving clinical outcomes for patients treated with radiation therapy. The roles of image guidance, adaptive ...planning and magnetic resonance imaging in radiation therapy have been increasing over the last two decades. Technical advances have led to the feasible combination of magnetic resonance imaging and radiation therapy technologies, leading to improved soft‐tissue visualisation, assessment of inter‐ and intrafraction motion, motion management, online adaptive radiation therapy and the incorporation of functional information into treatment. MRgRT can potentially transform radiation oncology by improving tumour control and quality of life after radiation therapy and increasing convenience of treatment by shortening treatment courses for patients. Multiple groups have developed clinical implementations of MRgRT predominantly in the abdomen and pelvis, with patients having been treated since 2014. While studies of MRgRT have primarily been dosimetric so far, an increasing number of trials are underway examining the potential clinical benefits of MRgRT, with coordinated efforts to rigorously evaluate the benefits of the promising technology. This review discusses the current implementations, studies, potential benefits and challenges of MRgRT.
Brachytherapy (BT), using low-dose-rate (LDR) permanent seed implantation or high-dose-rate (HDR) temporary source implantation, is an acceptable treatment option for select patients with prostate ...cancer of any risk group. The benefits of HDR-BT over LDR-BT include the ability to use the same source for other cancers, lower operator dependence, and - typically - fewer acute irritative symptoms. By contrast, the benefits of LDR-BT include more favourable scheduling logistics, lower initial capital equipment costs, no need for a shielded room, completion in a single implant, and more robust data from clinical trials. Prospective reports comparing HDR-BT and LDR-BT to each other or to other treatment options (such as external beam radiotherapy (EBRT) or surgery) suggest similar outcomes. The 5-year freedom from biochemical failure rates for patients with low-risk, intermediate-risk, and high-risk disease are >85%, 69-97%, and 63-80%, respectively. Brachytherapy with EBRT (versus brachytherapy alone) is an appropriate approach in select patients with intermediate-risk and high-risk disease. The 10-year rates of overall survival, distant metastasis, and cancer-specific mortality are >85%, <10%, and <5%, respectively. Grade 3-4 toxicities associated with HDR-BT and LDR-BT are rare, at <4% in most series, and quality of life is improved in patients who receive brachytherapy compared with those who undergo surgery.
Summary Background Follicular lymphoma has been shown to be highly radiosensitive with responses to doses as low as 4 Gy in two fractions. This trial was designed to explore the dose response for ...follicular lymphoma comparing 4 Gy in two fractions with 24 Gy in 12 fractions Methods FORT is a prospective randomised, unblinded, phase 3 non-inferiority study comparing radiotherapy given as 4 Gy in two fractions with a standard dose of 24 Gy in 12 fractions. Entry criteria included all patients aged over 18 years, having local radiotherapy for radical or palliative local control, with follicular lymphoma or marginal zone lymphoma, who had received no previous treatment for at least 1 month before. The primary outcome was time to local progression analysed on an intention-to-treat basis. Randomisation was centralised through the Cancer Research UK and University College London Cancer Trials Centre. Radiotherapy target sites were randomised (1:1) with minimisation stratified by histology (follicular lymphoma vs marginal zone lymphoma), treatment intent (palliative or curative) and centre. This trial is registered with ClinicalTrials.gov number, NCT00310167. Findings 299 sites were randomly assigned to 24 Gy and 315 sites to 4 Gy between April 7, 2006, and June 8, 2011, at 43 centres in the UK. After a median follow-up of 26 months (range 0·39–75·4), 91 local progressions had been recorded (21 in the 24 Gy group and 70 in the 4 Gy group). Time to local progression with 4 Gy was not non-inferior to 24 Gy (hazard ratio 3·42, 95% CI 2·09–5·55, p<0·0001). Eight (3%) of 282 patients in the 24 Gy group and four (1%) of 300 in the 4 Gy group had acute grade 3–4 toxic effects. Four (1%) patients in the 24 Gy group and four (1%) patients in the 4 Gy group had late toxic effects. Mucositis was the most common event in the 24 Gy group (two patients with acute mucositis and two with late mucositis; all grade 3) and was not reported in the 4 Gy group. The most common acute effect was pain at the site of irradiation (two patients in the 4 Gy group, one patient in the 24 Gy group; all grade 3), and the most common late effect was fatigue (two patients in the 4 Gy group, one patient in the 24 Gy group; all grade 3). Interpretation 24 Gy in 12 fractions is the more effective radiation schedule for indolent lymphoma and should be regarded as the standard of care. However, 4 Gy remains a useful alternative for palliative treatment. Funding Cancer Research UK.
Background: Delivered radiotherapy doses do not exactly match those planned for a course of treatment, largely due to inter-fraction changes in anatomy. In this study, accumulated delivered dose was ...calculated for a sample of cervical cancer patients, by deformably registering daily cone beam computed tomography (CBCT) images to the planning computed tomography (CT) scan. Planned and accumulated doses were compared for the clinical target volume (CTV), bladder, and rectum.
Material and Methods: For 10 patients receiving 45 Gy in 25 fractions of external beam radiotherapy, daily dose distributions were calculated on CBCT. These images were deformed onto the planning CT and the dose was accumulated using Velocity 4.1 (Varian Medical Systems, Palo Alto, USA). The quality of deformable image registration was evaluated visually and by calculating Dice similarity coefficients and mean distance to agreement.
Results: V95%>99% was achieved for the primary CTV in 9/10 patients for the planned dose distribution and 7/10 patients for the accumulated dose distribution. Primary CTV coverage by 95% of the prescription dose was reduced in one patient, due to an increase in anterior-posterior separation. Comparison of planned and accumulated dose volume histograms (DVHs) for the bladder and rectum found agreement within 5% at low and intermediate doses, but differences exceeded 20% at higher doses. Direct addition of CBCT DVHs was seen to be a poor estimate for the accumulated DVH at higher doses.
Conclusion: Computation of delivered radiotherapy dose that accounts for inter-fraction anatomical changes is important for establishing dose-effect relationships. Updating delivered dose distributions after each fraction would support informed clinical decision making on any potential treatment interventions.
The contemporary management of early-stage Hodgkin lymphoma (ES-HL) involves balancing the risk of late adverse effects of radiotherapy against the increased risk of relapse if radiotherapy is ...omitted. This study provides information on the risk of radiation-related cardiovascular disease to help personalize the delivery of radiotherapy in ES-HL.
We predicted 30-year absolute cardiovascular risk from chemotherapy and involved field radiotherapy in patients who were positron emission tomography (PET)-negative following three cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapy within a UK randomized trial of PET-directed therapy for ES-HL. Cardiac and carotid radiation doses and chemotherapy exposure were combined with established dose-response relationships and population-based mortality and incidence rates.
Average mean heart dose was 4.0 Gy (range 0.1-24.0 Gy) and average bilateral common carotid artery dose was 21.5 Gy (range 0.6-38.1 Gy), based on individualized cardiovascular dosimetry for 144 PET-negative patients receiving involved field radiotherapy. The average predicted 30-year radiation-related absolute excess overall cardiovascular mortality was 0.56% (range 0.01%-6.79%; < 0.5% in 67% of patients and > 1% in 15%), whereas average predicted 30-year excess incidence was 6.24% (range 0.31%-31.09%; < 5% in 58% of patients and > 10% in 24%). For cardiac disease, the average predicted 30-year radiation-related absolute excess mortality was 0.42% (0.79% with mediastinal involvement and 0.05% without) and for stroke, it was 0.14%.
Predicted excess cardiovascular risk is small for most patients, so radiotherapy may provide net benefit. However, for a minority of patients receiving high doses of radiation to cardiovascular structures, it may be preferable to consider advanced radiotherapy techniques to reduce doses or to omit radiotherapy and accept the increased relapse risk. Individual assessment of cardiovascular and other risks before treatment would allow personalized decision making about radiotherapy in ES-HL.
PDF
