Publications by authors named "Melanie Davidson"

49 Publications

Gantry-based 5-fraction Elective Nodal Irradiation in Unfavorable-Risk Prostate Cancer: Outcomes from 2 Prospective Studies comparing SABR Boost with MR Dose Painted HDR Brachytherapy Boost.

Int J Radiat Oncol Biol Phys 2021 Oct 9. Epub 2021 Oct 9.

Odette Cancer Centre, Sunnybrook Health Sciences Centre; Department of Radiation Oncology, University of Toronto; Institute of Health Policy, Management and Evaluation. Electronic address:

Background: ASCO/CCO guidelines recommend brachytherapy boost for intermediate-risk (IR) or high-risk (HR) prostate cancer (PCa) patients. Stereotactic ablative body radiotherapy (SABR) is an emerging technique for PCa but its use in HR disease is limited. We compare efficacy, toxicity, and quality-of-life (QoL) in patients treated on 2 prospective protocols that used SABR boost or MR-guided HDR brachytherapy boost (MR-HDR) with 6-18 months of androgen deprivation therapy (ADT).

Methods: In XXXXXX study (study 1), patients received 40Gy to prostate and 25Gy to pelvis in 5 weekly fractions. In XXXXXX (study 2), patients received HDR-BT 15Gy x 1 to the prostate and ≤22.5Gy to the MRI nodule, followed by 25Gy in 5 weekly fractions to pelvis. All patients received between 6 and 18 months of androgen deprivation therapy.

Results: Thirty patients (NCCN 7% unfavorable IR, and 93% HR) completed study 1 while 31 patients (NCCN 3% favorable IR, 47% Unfavorable IR and 50% HR) completed treatment as per study 2. Median follow-up was 72 and 62 months, respectively. In study 2, 6 patients had BF and all 6 developed metastatic disease. Actuarial 5-year BF was 0% for study 1 and 18.2% for study 2 (p=0.005). There was no significant difference in worst acute or late GI or GU toxicity. Grade 3 late GU toxicity was noted in 3% of the patients in study 2 (HDR-BT boost). There was no significant difference in QoL or minimally clinical important change.

Conclusions: In the context of 5-fraction pelvic radiotherapy and ADT, there does not appear to be a significant difference in toxicity or QoL between SABR vs. HDR BT boost. While efficacy favored the SABR boost cohort, this should be viewed in the context of limitations and biases associated with comparing two sequential phase II studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijrobp.2021.10.003DOI Listing
October 2021

Elective nodal ultra hypofractionated radiation for prostate cancer: Safety and efficacy from four prospective clinical trials.

Radiother Oncol 2021 Sep 4;163:159-164. Epub 2021 Sep 4.

Odette Cancer Centre, Sunnybrook Health Sciences Centre, Canada; Department of Radiation Oncology, University of Toronto, Canada; Institute of Health Policy, Management and Evaluation, Canada. Electronic address:

Background And Purpose: The role of elective nodal irradiation (ENI) in localized prostate cancer (PCa) is controversial. With increasing use of SBRT to the prostate, data is needed regarding the safety and efficacy of ENI using ultra-hypofractionated radiation (UHRT).

Materials And Methods: Between 2013-2020, 4 prospective clinical trials of intermediate or high-risk PCa receiving dose-escalated RT to the prostate (via HDR brachytherapy or SBRT boost) and ENI using UHRT (25 Gy in 5 weekly fractions) were conducted. Primary endpoints included acute genitourinary and gastrointestinal toxicities (CTCAE v3.0/4.0), and secondary endpoints included late genitourinary and gastrointestinal toxicities, patient-reported quality of life (EPIC) and biochemical failure (Phoenix definition).

Results: One-hundred sixty-five patients were enrolled, of whom 98 (59%) had high-risk disease. ADT was used in 141 (85%). Median follow-up was 38 months (IQR 10-63). The worst acute genitourinary and gastrointestinal toxicities respectively were 48% and 7.5% for grade 2, and 2.7% and 0% for grade 3. Cumulative incidence of late grade 2+ genitourinary and gastrointestinal toxicities at 36 months were 58% and 11.3% and for late grade 3+ toxicities were 1% and 0%, respectively. No grade 4+ acute or late toxicities were observed. Bowel and sexual toxicity significantly worsened up to 1-year compared to baseline. Over time, urinary (p < 0.0001), bowel (p = 0.0018) and sexual (p < 0.0001) scores significantly improved. The 3-year biochemical recurrence-free survival was 98%.

Conclusion: ENI using UHRT is associated with low incidence of grade 3+ toxicity, while grade 1-2 acute genitourinary and gastrointestinal toxicity is common. Randomized phase 3 trials are needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.radonc.2021.08.017DOI Listing
September 2021

Moving Unfavorable Small-Bowel Anatomy Away From the Prostate to Optimize Radiation Therapy Plans With the GU-Lok.

Pract Radiat Oncol 2021 Jul 5. Epub 2021 Jul 5.

Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada; Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada. Electronic address:

Patients with localized prostate cancer comprise a large volume of treatments in radiation therapy centers. Occasionally, individual patient anatomy makes the safe delivery of an effective dose of radiation therapy challenging. We describe 2 cases of patients with a small bowel deep in the pelvis within the planning target volume with subsequent suboptimal radiation therapy treatment plans. We explore how we used the GU-Lok, a prostate immobilization device, to move the small bowel away from the prostate, and tighten target volume margins to help facilitate safe and effective treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.prro.2021.06.009DOI Listing
July 2021

Stereotactic pelvic radiotherapy with HDR boost for dose escalation in intermediate and high-risk prostate cancer (SPARE): Efficacy, toxicity and quality of life.

Radiother Oncol 2021 08 3;161:40-46. Epub 2021 Jun 3.

Odette Cancer Centre, Sunnybrook Health Sciences Centre, Canada; Department of Radiation Oncology, University of Toronto, Canada; Institute of Health Policy, Management and Evaluation, Canada. Electronic address:

Background: The ASCO/CCO guidelines recommend brachytherapy (BT) boost for eligible intermediate- (IR) or high-risk (HR) prostate cancer (PCa) patients. We present efficacy, toxicity and quality-of-life (QoL) outcomes in patients treated on a prospective protocol of MRI dose-painted high-dose-rate BT boost (HDR-BT) followed by 5-fraction pelvic radiotherapy (RT) and 6-18 months of androgen deprivation therapy (ADT).

Methods: In this phase I/II study, IR or HR PCa patients received HDR-BT 15 Gy × 1 to prostate and up to 22.5 Gy to MRI nodule, followed by 25 Gy in 5, weekly fractions to pelvis. Toxicity was assessed using CTCAEv3.0, and QoL was captured using EPIC questionnaire. Biochemical failure (BF; nadir + 2.0), and proportion of patients with PSA < 0.4 ng/ml at 4-years (4yPSARR) were evaluated. A minimally clinically important change (MCIC) was recorded if QoL score decreased >0.5 standard deviation of baseline scores.

Results: Thirty-one patients (NCCN 3.2% favorable IR, 48.4% unfavorable IR and 48.4% HR) completed treatment with a median follow-up of 61 months. Median D90 to MR nodule was 19.0 Gy and median prostate V100% was 96.5%. The actuarial 5-year BF rate was 18.2%, and the 4yPSARR was 71%. One patient died of PCa. Acute grade 2 and 3 toxicities: GU: 50%, 7%, and GI: 3%, none, respectively. Late grade 2 and 3 toxicities were: GU: 23%, 3%, and GI: 7%, none, respectively. Proportion of patients with MCIC was 7.7% for urinary domain and 32.0% for bowel domain.

Conclusions: This novel treatment protocol incorporating MRI dose-painted HDR-BT boost and 5-fraction pelvic RT with ADT is well tolerated.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.radonc.2021.05.024DOI Listing
August 2021

Visually and olfactorily enhanced attractive devices for thrips management.

Entomol Exp Appl 2020 Sep 27;168(9):665-677. Epub 2020 Sep 27.

Wageningen University and Research PO Box 69 Wageningen 6700 AB The Netherlands.

'Lure-and-infect' is an insect pest management strategy with high potential but so far there are few examples of its application. Using traps as surrogates for auto-dissemination devices, we tested the attractiveness to naturally occurring thrips (Thysanoptera: Thripidae) of three trap types differing in colour and structure, with and without the thrips lure methyl isonicotinate (MI), and sticky plate traps as a control. The aim was to find more effective traps that could be further developed into devices for auto-dissemination and lure-and-infect of thrips. The number of thrips captured varied substantially with trap type and the presence of the MI lure. We found a high visual response to a sticky 'white ruffle' trap (i.e., a 30-cm-long cylindrical outline of folded fabric), compared to a commonly used blue sticky plate trap (Bug-scan) as the control. This effect was seen both in a greenhouse with roses ( spp.), where we encountered western flower thrips, (Pergande), and in a grass field, where we encountered onion thrips, Lindeman, and New Zealand flower thrips, (Crawford). In the absence of MI, the white ruffle trap caught 7-22× more thrips than the control Bug-scan trap. A similarly designed blue ruffle trap and a modified Lynfield trap caught lower thrips numbers than the white ruffle and the control Bug-scan traps. Presence of MI substantially increased the captures of in all three trap types in the field (2.5-18×). In the greenhouse, without MI the white ruffle trap caught 3.5-14× more thrips than the Bug-scan, blue ruffle, or modified Lynfield traps. Presence of MI increased the captures of males and females in the Lynfield and blue ruffle traps (1.4-2.8×), but not in the white ruffle trap in the greenhouse (ca. 1.1×). The importance of visual and olfactory factors for the design of effective auto-dissemination and lure-and-infect strategies for thrips management is discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/eea.12969DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7594531PMC
September 2020

Dosimetric evaluation of MRI-to-ultrasound automated image registration algorithms for prostate brachytherapy.

Brachytherapy 2020 Sep - Oct;19(5):599-606. Epub 2020 Jul 22.

Department of Medical Physics, University of Toronto, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada. Electronic address:

Purpose: Identifying dominant intraprostatic lesions (DILs) on transrectal ultrasound (TRUS) images during prostate high-dose-rate brachytherapy treatment planning remains a significant challenge. Multiparametric MRI (mpMRI) is the tool of choice for DIL identification; however, the geometry of the prostate on mpMRI and on the TRUS may differ significantly, requiring image registration. This study assesses the dosimetric impact attributed to differences in DIL contours generated using commonly available MRI to TRUS automated registration: rigid, semi-rigid, and deformable image registration, respectively.

Methods And Materials: Ten patients, each with mpMRI and TRUS data sets, were included in this study. Five radiation oncologists with expertise in TRUS-based high-dose-rate brachytherapy were asked cognitively to transfer the DIL from the mpMRI images of each patient to the TRUS image. The contours were analyzed for concordance using simultaneous truth and performance level estimation (STAPLE) algorithm. The impact of DIL contour differences due to registration variability was evaluated by comparing the STAPLE-DIL dosimetry from the reference (STAPLE) plan with that from the evaluation plans (manual and automated registration) for each patient. The dosimetric impact of the automatic registration approach was also validated using a margin expansion that normalizes the volume of the autoregistered DILs to the volumes of the STAPLE-DILs. Dose metrics including D, D, V, and V to the prostate and DIL were reported. For urethra and rectum, D and V were reported.

Results: Significant differences in DIL coverage between reference and evaluation plans were found regardless of the algorithm methodology. No statistical difference was reported in STAPLE-DIL dosimetry when manual registration was used. A margin of 1.5 ± 0.8 mm, 1.1 ± 0.8 mm, and 2.5 ± 1.6 mm was required to be added for rigid, semi-rigid, and deformable registration, respectively, to mitigate the difference in STAPLE-DIL coverage between the evaluation and reference plans.

Conclusion: The dosimetric impact of integrating an MRI-delineated DIL into a TRUS-based brachytherapy workflow has been validated in this study. The results show that rigid, semi-rigid, and deformable registration algorithms lead to a significant undercoverage of the DIL D and D. A margin of at least 1.5 ± 0.8 mm, 1.1 ± 0.8 mm, and 2.5 ± 1.6 mm is required to be added to the rigid, semi-rigid, and deformable DIL registration to be suitable for DIL-boosting during prostate brachytherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.brachy.2020.06.014DOI Listing
May 2021

Should we embrace hypofractionated radiotherapy for cervical cancer? A technical note on management during the COVID-19 pandemic.

Radiother Oncol 2020 07 28;148:270-273. Epub 2020 May 28.

University of Toronto, Department of Radiation Oncology, Canada; Sunnybrook Health Sciences Centre, Toronto, Canada.

Cervical cancer is a deadly disease and the COVID-19 pandemic has the potential to further impact its lethality. Hypofractionated radiotherapy could mitigate this impact, however robust data in cervical cancer setting still is lacking. Information provided here could help institutions in reducing radiotherapy fractions for cervical cancer patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.radonc.2020.05.032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7255703PMC
July 2020

Accelerating prostate stereotactic ablative body radiotherapy: Efficacy and toxicity of a randomized phase II study of 11 versus 29 days overall treatment time (PATRIOT).

Radiother Oncol 2020 08 27;149:8-13. Epub 2020 Apr 27.

Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Canada; Institute of Health Policy Management and Evaluation, University of Toronto, Canada. Electronic address:

Background: Prostate stereotactic ablative radiotherapy (SABR) regimens differ in time, dose, and fractionation. We report an update of a multicentre, Canadian randomized phase II study to investigate the impact of overall treatment time on quality of life (QOL), efficacy, and toxicity.

Methods: Men with intermediate risk prostate cancer were randomized to 40 Gy in 5 fractions delivered every other day (EOD) versus once per week (QW). Primary outcome was proportion of patients experiencing a minimally clinically important change (MCIC) in acute bowel QOL using EPIC. Secondary outcomes were toxicity, biochemical failure (BF), other QOL domains, and the rate of salvage therapy.

Findings: 152 men from 3 centers were randomized; the median follow-up was 62 months. Results are described for EOD versus QW. Acute bowel and urinary QOL was reported previously. Late changes in QOL were not significantly different between the two arms. There were 1 (1.3%) vs 3 (2.7%) late grade 3 + GI toxicities (p = 0.36) and 5 (6.7%) vs 2 (2.7%) late grade 3 GU toxicities (p = 0.44). Two and 5 patients had BF (5-year failure rate 3.0 vs 7.2%, p = 0.22); 0 and 4 patients received salvage therapy (p = 0.04). 5-Year OS and CSS was 95.8% and 98.6% with no difference between arms (p = 0.49, p = 0.15). 3 patients in the QW arm developed metastases.

Interpretation: Although we previously reported that weekly prostate SABR had better bowel and urinary QOL compared to EOD, the updated results show no difference in late toxicity, QOL, BF, or PSA kinetics. Patients should be counseled that QW SABR reduces short-term toxicity compared to QW SABR.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.radonc.2020.04.039DOI Listing
August 2020

Conventional vs machine learning-based treatment planning in prostate brachytherapy: Results of a Phase I randomized controlled trial.

Brachytherapy 2020 Jul - Aug;19(4):470-476. Epub 2020 Apr 19.

Department of Medical Physics, Sunnybrook Odette Cancer Centre, Toronto, ON, Canada. Electronic address:

Purpose: The purpose of this study was to evaluate the noninferiority of Day 30 dosimetry between a machine learning-based treatment planning system for prostate low-dose-rate (LDR) brachytherapy and the conventional, manual planning technique. As a secondary objective, the impact of planning technique on clinical workflow efficiency was also evaluated.

Materials And Methods: 41 consecutive patients who underwent I-125 LDR monotherapy for low- and intermediate-risk prostate cancer were accrued into this single-institution study between 2017 and 2018. Patients were 1:1 randomized to receive treatment planning using a machine learning-based prostate implant planning algorithm (PIPA system) or conventional, manual technique. Treatment plan modifications by the radiation oncologist were evaluated by computing the Dice coefficient of the prostate V isodose volume between either the PIPA-or conventional-and final approved plans. Additional evaluations between groups evaluated the total planning time and dosimetric outcomes at preimplant and Day 30.

Results: 21 and 20 patients were treated using the PIPA and conventional techniques, respectively. No significant differences were observed in preimplant or Day 30 prostate D, V, rectum V, or rectum D between PIPA and conventional techniques. Although the PIPA group had a larger proportion of patients with plans requiring no modifications (Dice = 1.00), there was no significant difference between the magnitude of modifications between each arm. There was a large significant advantage in mean planning time for the PIPA arm (2.38 ± 0.96 min) compared with the conventional (43.13 ± 58.70 min) technique (p >> 0.05).

Conclusions: A machine learning-based planning workflow for prostate LDR brachytherapy has the potential to offer significant time savings and operational efficiencies, while producing noninferior postoperative dosimetry to that of expert, conventional treatment planners.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.brachy.2020.03.004DOI Listing
April 2021

Evaluating the Tolerability of a Simultaneous Focal Boost to the Gross Tumor in Prostate SABR: A Toxicity and Quality-of-Life Comparison of Two Prospective Trials.

Int J Radiat Oncol Biol Phys 2020 05 25;107(1):136-142. Epub 2020 Jan 25.

Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada. Electronic address:

Purpose: Dose-escalated stereotactic ablative radiotherapy (SABR) to the whole prostate may be associated with better outcomes but has a risk of increased toxicity. An alternative approach is to focally boost the dominant intraprostatic lesion (DIL) seen on magnetic resonance imaging. We report the toxicity and quality-of-life (QOL) outcomes of 2 phase 2 trials of prostate and pelvic SABR, with or without a simultaneous DIL boost.

Methods And Materials: The first trial treated patients with high-risk prostate cancer to a dose of 40 Gy to the prostate and 25 Gy to the pelvis in 5 fractions. The second trial treated patients with intermediate-risk and high-risk prostate cancer to a dose of 35 Gy to the prostate, 25 Gy to the pelvis, and a DIL boost up to 50 Gy in 5 fractions. Acute toxicities, late toxicities, and QOL were assessed.

Results: Thirty patients were enrolled in each trial. In the focal boost cohort, the median DIL D90% was 48.3 Gy. There was no significant difference in acute grade ≥2 gastrointestinal or genitourinary toxicity between the 2 trials or in cumulative worst late gastrointestinal or genitourinary toxicity up to 24 months. There was no significant difference in QOL domain scores or minimally clinical important change between the 2 trials.

Conclusions: Prostate and pelvic SABR with a simultaneous DIL boost was feasible. Acute grade ≥2 toxicity, late toxicity, and QOL seemed to be comparable to a cohort that did not receive a focal boost. Further follow-up will be required to assess long-term outcomes, and randomized data are required to confirm these findings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijrobp.2019.12.044DOI Listing
May 2020

Patient Experiences in Canadian Hospitals.

Healthc Q 2019 Oct;22(3):12-14

Naomi Diestelkamp, is a senior analyst at CIHI, Toronto, ON.

With its first release of patient experience data, the Canadian Institute for Health Information provides a high-level summary of results from the Canadian Patient Experiences Survey - Inpatient Care captured in the Canadian Patient Experiences Reporting System. It examines how Canadian patients feel about how information was communicated and shared at different stages of their hospital stay.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12927/hcq.2019.26024DOI Listing
October 2019

Dosimetric predictors of toxicity and quality of life following prostate stereotactic ablative radiotherapy.

Radiother Oncol 2020 03 3;144:135-140. Epub 2019 Dec 3.

Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Canada; Institute of Health Policy Management and Evaluation, University of Toronto, Canada. Electronic address:

Purpose: SABR offers an effective treatment option for clinically localized prostate cancer. Here we report the dosimetric predictors of late toxicity and quality of life (QOL) in a pooled cohort of patients from four phase II trials.

Methods: The combined cohort included all three prostate cancer risk groups. The prescription dose was 35-40 Gy in 5 fractions. Toxicity (CTCAE) and QOL (EPIC) were collected. Multiple dosimetric parameters for the bladder, rectum and penile bulb were collected. Univariate (UVA) followed by multivariate (MVA) logistic regression analysis was conducted to search for significant dosimetric predictors of late GI/GU toxicity, or minimal clinically important change in the relevant QOL domain.

Results: 258 patients were included with median follow up of 6.1 years. For QOL, bladder Dmax, V38, D1cc, D2cc, D5cc and rectal V35 were predictors of urinary and bowel MCIC on UVA. On MVA, only bladder V38 remained significant. For late toxicity, various parameters were significant on UVA but only rectal Dmax, V38 and bladder D2cc were significant predictors on MVA.

Conclusions: This report confirms that the high-dose regions in the bladder and rectum are more significant predictors of late toxicity and QOL after prostate SABR compared to low-dose regions. Caution must be taken to avoid high doses and hotspots in those organs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.radonc.2019.11.017DOI Listing
March 2020

Two versus five stereotactic ablative radiotherapy treatments for localized prostate cancer: A quality of life analysis of two prospective clinical trials.

Radiother Oncol 2019 11 29;140:105-109. Epub 2019 Jun 29.

Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Canada; Department of Radiation Oncology, University of Toronto, Canada. Electronic address:

Purpose: Stereotactic ablative radiotherapy (SABR) is appealing for prostate cancer (PCa) due to low α/β, and increasing the dose per fraction could improve the therapeutic index and lead to a better quality of life (QOL). Here we report the outcomes of a QOL comparison between two phase II clinical trials: two vs. five fraction prostate SABR.

Methods: Patients had low or intermediate risk PCa. The doses prescribed were 26 Gy/2 and 40 Gy/5. Expanded prostate cancer index composite was collected. Urinary, bowel and sexual domains were analyzed. Minimal clinically important change (MCIC) was defined as >0.5 standard deviation.

Results: 30 and 152 patients were treated with 2-fraction and 5-fraction SABR. Median follow-up was 55 and 62 months. Five-year biochemical failure rate was 3.3% and 4.6%. The 2-fraction cohort had a significantly better mean QOL over time in the bowel domain (p = 0.0004), without a significant difference in the urinary or sexual domains. The 2-fraction cohort had a significantly lower rate of bowel MCIC (17.8% vs 42.3%, p = 0.01), but there was no difference in urinary (24.1% vs 35.7%) or sexual (15.3% vs 29.2%) MCIC. For MCIC x2 (moderate QOL change), the 2-fraction trial had significantly lower MCIC rates in both the bowel (7.1% vs 24%, p = 0.04) and sexual (0 vs 17.6%, p = 0.01) domains.

Conclusions: 2-Fraction SABR is feasible to deliver and well tolerated, with significant signals of improved bowel and sexual QOL. A randomized trial of two vs. five fractions for prostate SABR is needed to confirm the promising findings of this study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.radonc.2019.06.018DOI Listing
November 2019

Two StereoTactic ablative radiotherapy treatments for localized prostate cancer (2STAR): Results from a prospective clinical trial.

Radiother Oncol 2019 06 19;135:86-90. Epub 2019 Mar 19.

Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Canada; Department of Radiation Oncology, University of Toronto, Canada; Department of Health Policy, Measurement and Evaluation, University of Toronto, Canada. Electronic address:

Purpose: Ultrahypofractionation is appealing for prostate cancer (PCa) due to low α/β, and increasing the dose per fraction could improve the therapeutic index. Here we report the outcomes of a phase II prostate SABR trial using two fractions.

Methods: Patients had low or intermediate risk prostate cancer. Three gold fiducials were implanted for image guidance. The clinical target volume (CTV) included the prostate only, and the planning target volume (PTV) was a 3 mm expansion enabled through the use of a rectal immobilization device. The dose prescribed was 26 Gy in 2 weekly fractions (EQD2 110 Gy). The primary endpoint was quality of life using EPIC, and minimal clinically important change (MCIC) was defined as an EPIC QOL decrease >0.5 SD.

Results: 30 patients were accrued with a median follow-up of 49.3 months. 10% had low-risk, 33% had favourable intermediate-risk and 57% had unfavourable intermediate-risk PCa. Five patients received a short course of ADT. Median nPSA was 0.2 ng/ml. One patient had BF and is being observed. 56.6% of patients had a 4yPSARR. Six (20.7%) patients had a MCIC in the urinary domain, 6 (21.4%) had a MCIC in the bowel domain, and 3 (20%) had a MCIC in the sexual domain.

Conclusions: Two-fraction SABR in prostate cancer is safe and feasible, with a minimal change in QOL and a low rate of late grade 3-4 toxicity. The PSA kinetics and biochemical control rates are encouraging given that the majority had unfavourable intermediate-risk disease, although longer follow-up is required.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.radonc.2019.03.002DOI Listing
June 2019

Stereotactic Body Radiation Therapy Boost for Intermediate-Risk Prostate Cancer: A Phase 1 Dose-Escalation Study.

Int J Radiat Oncol Biol Phys 2019 08 16;104(5):1066-1073. Epub 2019 Apr 16.

Sunnybrook Health Sciences Centre-Odette Cancer Centre, Toronto, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Canada. Electronic address:

Purpose: High-dose-rate brachytherapy boost plus external beam radiation therapy is an established option for intermediate-risk prostate cancer (PCa). Stereotactic body radiation therapy (SBRT) boost can potentially mimic high-dose-rate boost and could be a viable alternative. Here we report the long-term outcomes of a phase 1 dose-escalation trial of single-fraction SBRT boost.

Methods And Materials: Patients had intermediate-risk PCa and were accrued to 3 different SBRT single-fraction dose-level cohorts (10 Gy, 12.5 Gy, and 15 Gy). All received supplemental radiation therapy afterwards (37.5 Gy in 15 fractions). Three gold fiducials were implanted for image guidance. Patients were simulated and treated with a foley catheter and intrarectal balloon. A T2 magnetic resonance imaging scan was used for contouring, and a cine magnetic resonance imaging scan was used to calculate patient-specific internal target volume margins. Toxicity and quality-of-life data were collected using Common Terminology Criteria for Adverse Events v3.0 and the Expanded Prostate Cancer Index Composite.

Results: 30 patients were accrued, 10 in each cohort. Median follow-up was 72 months. 60% had unfavorable intermediate-risk PCa. Two patients in the 15 Gy cohort developed late grade ≥3 gastrointestinal and genitourinary toxicity, with 1 patient suffering from a grade-4 rectal fistula after a rectal ulcer was biopsied repeatedly. Two patients had biochemical failure. Median PSA nadir was 0.4 ng/mL with 10 Gy, 0.09 ng/mL with 12.5 Gy and 0.07 ng/mL with 15 Gy. Median PSA at 4 years as well as proportion achieving a nadir <0.2 ng/mL improved significantly with higher doses. There was no significant change in quality of life from baseline in any of the domains, and the minimal clinically important change was not statistically different between the 3 cohorts.

Conclusions: Other than a grade 4 toxicity, which may in part be due to repeated biopsies of a rectal ulcer, single-fraction SBRT boost was feasible and well tolerated. Larger studies are warranted to better document the outcomes of such an approach.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijrobp.2019.04.006DOI Listing
August 2019

SABR in High-Risk Prostate Cancer: Outcomes From 2 Prospective Clinical Trials With and Without Elective Nodal Irradiation.

Int J Radiat Oncol Biol Phys 2019 05 14;104(1):36-41. Epub 2018 Nov 14.

Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Canada; Department of Health Policy, Measurement and Evaluation, University of Toronto, Toronto, Canada. Electronic address:

Purpose: There is limited data on stereotactic ablative radiation therapy (SABR) in high-risk prostate cancer (PCa), especially regarding the role of elective nodal irradiation (ENI). This study compares 2 prospective phase 2 trials using SABR in high-risk PCa, with and without ENI.

Methods And Materials: Patients had high-risk PCa. Those in trial 1 received 40 Gy in 5 fractions to the prostate and 30 Gy in 5 fractions to the seminal vesicles. Patients in trial 2 received 40 Gy in 5 fractions to the prostate and 25 Gy in 5 fractions to the pelvis and seminal vesicles. National Cancer Institute Common Terminology Criteria for Adverse Events toxicities were collected. Biochemical failure (BF) was defined as nadir + 2, and the 4-year prostate-specific antigen (PSA) response rate (4yPSARR) was <0.4 ng/mL.

Results: Sixty patients were included (trial 1, n = 30; trial 2, n = 30). Median follow-up was 5.6 years and 4.0 years. The median nadir PSA was 0.02 ng/mL for both trials. Six patients had BF, all from trial 1. The BF rate was 14.6% at 5 years in trial 1 and 0% in trial 2. Sixty-three percent of patients in trial 1 and 93% in trial 2 had a 4yPSARR. Two patients died in trial 1, 1 from metastatic disease. One patient in trial 2 died of other causes. No other patients developed metastatic disease, and 1 patient in trial 1 had castrate resistant PCa. Overall survival at 5 years was 93.2% and 96.7% (P = .86). There was significantly worse late gastrointestinal and sexual toxicity in trial 1, but there was no difference in late genitourinary toxicity.

Conclusions: SABR in high-risk PCa yields biochemical control rates that may be comparable to that of other radiation therapy modalities. ENI using SABR is feasible and may lead to a significant improvement in biochemical control and in 4yPSARR, without an increase in late gastrointestinal or genitourinary toxicity. Longer follow-up would provide a better assessment of biochemical control. Well-conducted phase 3 trials are needed to fully establish the role of SABR and ENI in high-risk PCa.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijrobp.2018.11.011DOI Listing
May 2019

Clinical evaluation of an MRI-to-ultrasound deformable image registration algorithm for prostate brachytherapy.

Brachytherapy 2019 Jan - Feb;18(1):95-102. Epub 2018 Oct 2.

Department of Medical Physics, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada. Electronic address:

Purpose: Identifying dominant intraprostatic lesions (DILs) on transrectal ultrasound (TRUS) images during prostate high-dose-rate brachytherapy (HDR-BT) treatment planning is challenging. Multiparametric MRI (mpMRI) is the tool of choice for DIL identification; however, the geometry of the prostate on mpMRI and on the TRUS may differ significantly, requiring image registration. This study evaluates the efficacy of an in-house software for MRI-to-TRUS DIL registration (MR2US) and compares its results to rigid and B-Spline deformable registration.

Methods And Materials: Ten patients with intermediate-risk prostate cancer, each with mpMRI and TRUS data sets, were included in this study. Five radiation oncologists (ROs) with expertise in TRUS-based HDR-BT were asked to cognitively contour the DIL onto the TRUS image using mpMRI as reference. The contours were analyzed for concordance using simultaneous truth and performance level estimation algorithm. Similarity indices, DIL volumes, and distance between centroid positions were measured to compare the consensus contours against the contours from ROs and the automated algorithms; registration time between all contouring methods was recorded.

Results: MR2US registration had the highest dice coefficients among all patients with a mean of 0.80 ± 0.13 in comparison to rigid (0.65 ± 0.20) and B-Spline (0.51 ± 0.30). The distance between centroid positions between simultaneous truth and performance level estimation contour and MR2US, rigid, and B-Spline contours were 5 ± 2, 7 ± 5, and 18 ± 11 mm, respectively. The average registration time was significantly shorter for MR2US (11 ± 2 s) and rigid algorithm (7 ± 1 s) compared to ROs (227 ± 27 s) and B-Spline (199 ± 38 s).

Conclusions: The efficacy of integrating an MRI-delineated DIL into a TRUS-based BT workflow has been validated in this study. The MR2US software is fast and accurate enough to be used for DIL identification in prostate HDR-BT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.brachy.2018.08.006DOI Listing
April 2019

Quality of life changes after stereotactic ablative radiotherapy for liver metastases: A prospective cohort analysis.

Radiother Oncol 2018 12 28;129(3):435-440. Epub 2018 Sep 28.

Department of Radiation Oncology, University of Toronto, Sunnybrook Odette Cancer Centre, Canada. Electronic address:

Purpose: To report the changes in quality of life (QoL) after stereotactic ablative radiotherapy (SABR) in patients with liver metastases (LM).

Materials And Methods: A prospective cohort study was undertaken to measure the acute changes in QoL after SABR. Patients with 1-3 treated LM were eligible. Doses of 30-60 Gy in 3-5 fractions were delivered. Prospective QoL was measured using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaires, Core 15 for Palliative Care (EORTC QLQ-C15-PAL) and liver metastases (LM21), at baseline, 1st week and last day of treatment, then 1, 6 and 12 weeks after SABR. The functional living index-emesis (FLIE) was collected at baseline, 1st week, last day and 1 week after treatment. Univariable and multivariable linear mixed modeling were performed as appropriate to assess changes in QoL over time.

Results: Sixty patients were included. The most common primary cancer was colorectal (42%). The global health score measured by QLQ-C15-PAL was significantly worse at treatment completion (p = 0.001), 1 week (p = 0.003) and 6 weeks (p = 0.002) after SABR but recovered by 12 weeks (p = 0.124). Nausea and constipation were worse at treatment completion (p < 0.05) but recovered 1 week after while fatigue recovered 6 weeks post-SABR. The majority of patients reported stable QoL at 12 weeks for all domains in the C15-PAL and LM21 questionnaires.

Conclusion: SABR offers a non-invasive mean of ablating LM with minimal impact on acute QoL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.radonc.2018.09.011DOI Listing
December 2018

Focal Salvage High Dose-Rate Brachytherapy for Locally Recurrent Prostate Cancer After Primary Radiation Therapy Failure: Results From a Prospective Clinical Trial.

Int J Radiat Oncol Biol Phys 2018 11 2;102(3):561-567. Epub 2018 Jul 2.

Department of Radiation Oncology, Odette Cancer Center, Sunnybrook Health Sciences Center, Toronto, Ontario, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada. Electronic address:

Purpose: Although increasing data support whole-gland salvage therapy for recurrent prostate cancer, toxicity remains a significant concern. We hypothesized that focal therapy, treating only a portion of the prostate containing recurrent disease, might be equally effective and associated with less toxicity. The objectives of this prospective study were to explore the toxicities, quality of life, and efficacy of focal salvage high-dose-rate (HDR) brachytherapy in patients with multiparametric magnetic resonance imaging (MRI)-visible, biopsy-confirmed local recurrence after previous definitive external beam radiation therapy.

Materials And Methods: Fifteen patients with locally recurrent prostate cancer after external beam radiation therapy were enrolled in this prospective study. Patients were treated with ultrasound-based HDR brachytherapy with a prescription dose of 27 Gy divided in 2 implants, separated by 1 week, to the clinical target volume, which was defined as the quadrant of the prostate where the MRI-visible recurrent lesion was located. Toxicity, quality of life, and biochemical outcomes were analyzed. Postsalvage MRI was performed to assess radiation therapy response.

Results: Median follow-up was 36 months. The median size of the recurrence on MRI was 9 mm (range, 7-20 mm), and clinical target volume at the time of HDR was 6.1 mL (range, 2.2-16.1 mL). Only one grade 3 genitourinary toxicity event was observed. No urinary retention was observed. Three-year prostate-specific antigen failure-free rate was 61%. There was no significant change in Expanded Prostate Cancer Index Composite urinary or bowel domains over time. Of the 14 patients who had a post-HDR MRI, 12 had a treatment response.

Conclusions: Our results suggest that focal salvage HDR brachytherapy is well tolerated and promising. External validation is needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijrobp.2018.06.039DOI Listing
November 2018

A Feasibility Study on the Role of Ultrasound Imaging of Bladder Volume as a Method to Improve Concordance of Bladder Filling Status on Treatment with Simulation.

J Med Imaging Radiat Sci 2018 Sep 22;49(3):277-285. Epub 2018 Jun 22.

Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada; Department of Medical Physics, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada. Electronic address:

Purpose: Accurate positioning of the prostate is of paramount importance to ensure optimal target coverage and normal tissue sparing in stereotactic ablative body radiation when large doses per fraction are delivered with tight margins around the prostate. Bladder and rectal filling play an important part in controlling the accuracy of a patient's setup and therefore the overall toxicities and outcomes. The aim of this study was to establish the value of characterizing patients' bladder filling kinetics at the time of simulation with ultrasound scans so that a predictive model can be used to ensure that a bladder volume at treatment would match at simulation.

Methods: A prospective trial was conducted in unfavorable risk prostate cancer patients to evaluate the utility of ultrasound bladder monitoring. Thirty patients (n = 30) were enrolled in this study. Patients were required to void before simulation and then were given 500 mL of fluids to drink. Ultrasound measurements of the bladder were documented at 15-minute intervals for up to four measurements before simulation. On treatment, bladder volumes were measured at a single time point; typically, half an hour after the patient voided and consumed 500 mL of fluids. The kinetic model was then used to predict the optimal time to set up the patient for treatment such that the bladder volume at treatment would match the volume at simulation. Every patient had a cone beam computed tomography scan before each fraction to ensure accurate patient positioning before dose delivery. Bladder volumes at treatment were measured and compared with those at simulation on the cone beam computed tomography data sets using MIMVISTA software.

Results: Of 30 patients, 26 were analyzed. The comparison of the bladder contours at treatment compared to simulation yielded a DICE coefficient (similarity) of 0.76 ± 0.11. The largest variation in bladder size was seen in the anterior-posterior direction.

Conclusions: This study demonstrated that ultrasound monitoring of the bladder status was a valuable tool in ensuring reproducible bladder filling on treatment. The bladder kinetic model indicated the general time required to achieve optimal bladder filling was 60 minutes after voiding and drinking 500 mL of water.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jmir.2018.04.031DOI Listing
September 2018

Host plant influences establishment and performance of Amblydromalus limonicus, a predator for Bactericera cockerelli.

Pest Manag Sci 2019 Mar 28;75(3):787-792. Epub 2018 Sep 28.

Bioprotection, The New Zealand Institute for Plant & Food Research Limited, Christchurch, New Zealand.

Background: Management of tomato potato psyllid (TPP; Bactericera cockerelli (Šulc)) predominantly relies on insecticides. However, biological control agents (BCAs) could provide viable alternatives to suppress TPP populations. In this laboratory experiment, we assessed the predatory mite Amblydromalus limonicus (Garman & McGregor) as a BCA of TPP on whole plants of two tomato and two pepper cultivars over a 5-week period.

Results: Plant species and cultivar had a significant effect on the ability of A. limonicus to suppress populations of TPP. Numbers of TPP were suppressed by A. limonicus on four pepper treatments, but on only one tomato treatment. Amblydromalus limonicus could survive and reproduce on pepper and tomato, but more were found on pepper at the end of the 5-week period.

Conclusion: Amblydromalus limonicus has the potential to suppress TPP populations on pepper but not tomato cultivars, based on the present study. Possible reasons for these results include the difference in leaf morphology between species, and higher predator:prey ratios on pepper than tomato because of the longer TPP generation time on pepper. © 2018 Society of Chemical Industry.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ps.5179DOI Listing
March 2019

Phase 1-2 Study of Stereotactic Ablative Radiotherapy Including Regional Lymph Node Irradiation in Patients With High-Risk Prostate Cancer (SATURN): Early Toxicity and Quality of Life.

Int J Radiat Oncol Biol Phys 2018 12 31;102(5):1438-1447. Epub 2018 Jul 31.

Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada; Department of Health Policy, Measurement and Evaluation, University of Toronto, Toronto, Canada. Electronic address:

Purpose: Five-fraction stereotactic ablative radiation therapy appears to be gaining popularity in treatment of prostate cancer, but it has not been extensively tested in the context of pelvic radiation. The objective of this prospective prostate and pelvic SABR study is to report the acute toxicity, late toxicity, and quality of life (QoL) after study completion.

Methods And Materials: A phase 1/2 study was conducted for patients with high-risk prostate cancer. Radiation therapy was planned to deliver 25 Gy to pelvis and seminal vesicles (SV) and a simultaneous integrated boost (SIB) of up to 40 Gy to the prostate in 5 fractions, weekly, over 29 days. Androgen deprivation therapy was used for 12 to 18 months. Common Terminology Criteria for Adverse Events version 3.0 was used to assess worst acute and late toxicities. QoL data was captured using the Expanded Prostate Cancer Index Composite questionnaire (EPIC).

Results: Thirty patients completed the planned treatment with a median follow-up of 25.7 months (range, 18.5-30.7 months). The following "worst" acute and late toxicities were observed: grade 2 genitourinary toxicity, 46.7% and 52%, respectively; grade 2 gastrointestinal toxicity, 3.3% and 32%, respectively. No grade 3 or higher toxicities were noted. Mean (95% confidence interval) EPIC urinary QoL scores were 86.6 (81.9-91.3), 87.1 (81.4-92.6), and 87.9 (80.1-95.7) at baseline, 3 months and 24 months; bowel scores were 94.1 (91.3-97.0), 93.2 (89.1-97.2), and 92.4 (87.7- 97.1), respectively.

Conclusions: This gantry-based novel fractionation schedule incorporating pelvic radiation for high-risk prostate cancer in combination with androgen deprivation therapy is feasible and well tolerated.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijrobp.2018.07.2005DOI Listing
December 2018

Once-weekly versus every-other-day stereotactic body radiotherapy in patients with prostate cancer (PATRIOT): A phase 2 randomized trial.

Radiother Oncol 2018 May 15;127(2):206-212. Epub 2018 Mar 15.

Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Canada.

Background And Purpose: Prostate stereotactic body radiotherapy (SBRT) regimens differ in time, dose, and fractionation. We completed a multicentre, randomized phase II study to investigate the impact of overall treatment time on quality of life (QOL).

Material And Methods: Men with low and intermediate-risk prostate cancer were randomly assigned to 40 Gy in 5 fractions delivered once per week (QW) vs. every other day (EOD). QOL was assessed using the Expanded Prostate Cancer Index Composite. The primary endpoint was the proportion with a minimum clinically important change (MCIC) in bowel QOL during the acute (≤12 week) period, and analysis was by intention-to-treat. ClinicalTrials.gov NCT01423474.

Results: 152 men from 3 centres were randomized with median follow-up of 47 months. Patients treated QW had superior acute bowel QOL with 47/69 (68%) reporting a MCIC compared to 63/70 (90%) treated EOD (p = 0.002). Fewer patients treated QW reported moderate-severe problems with bowel QOL during the acute period compared with EOD (14/70 [20%] vs. 40/70 [57%], p < 0.001). Acute urinary QOL was also better in the QW arm, with 52/67 (78%) vs 65/69 (94%) experiencing a MCIC (p = 0.006). There were no significant differences in late urinary or bowel QOL at 2 years or last follow-up.

Conclusion: Prostate SBRT delivered QW improved acute bowel and urinary QOL compared to EOD. Patients should be counselled regarding the potential for reduced short-term toxicity and improved QOL with QW prostate SBRT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.radonc.2018.02.029DOI Listing
May 2018

Characterizing the impact of adaptive planning on image-guided perineal interstitial brachytherapy for gynecologic malignancies.

Brachytherapy 2018 Mar - Apr;17(2):352-359. Epub 2017 Dec 11.

Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada. Electronic address:

Purpose: To determine the dosimetric impact of organ and implant motion/deformation in the context of adaptive planning in image-guided gynecologic brachytherapy using a 3-fraction transperineal approach.

Methods And Materials: Twenty-six patients were analyzed. Each patient was treated with three fractions given over a 24-h period using a single insertion. A planning CT scan (±MRI) was acquired before the first fraction. A verification scan was taken within 1 h following the second fraction. A single plan was delivered for Fractions 1 and 2 with an adaptive plan delivered for Fraction 3. Two evaluation frameworks were established. Framework 1 investigated the effects of motion/deformation from both implant and organs. Framework 2 investigated the impact of implant motion/deformation alone. Differences in high-risk clinical target volume (HRCTV) D, V, and bladder/rectum D were assessed.

Results: From implant to verification, the HRCTV D and V decreased significantly (5.0%, p < 0.01; 3.1%, p < 0.01) and rectal D was significantly higher (12.2%, p = 0.02). Adaptive planning recouped these changes. Implant changes resulted in a reduction in HRCTV dose and coverage, but no significant effect was seen in the bladder or rectum.

Conclusions: Adaptive planning represents an important aspect of perineal-based interstitial image-guided brachytherapy given in three fractions; its absence would result in plan degradation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.brachy.2017.11.005DOI Listing
January 2019

Extreme hypofractionation for high-risk prostate cancer: Dosimetric correlations with rectal bleeding.

Pract Radiat Oncol 2017 Nov - Dec;7(6):e457-e462. Epub 2017 Jun 9.

Department of Radiation Oncology, Odette Cancer Centre and University of Toronto, Toronto, Ontario, Canada.

Purpose: We explored the association of dosimetric parameters with late rectal bleeding among high-risk prostate cancer patients treated with hypofractionated simultaneous in-field boost (H-SIB) to prostate with nodal treatment.

Methods And Materials: Rectal toxicity results and dose-volume histogram (DVH) information from patients treated on FASTR and SATURN were combined. Patients in both trials received long-term androgen deprivation and H-SIB with prescription dose 40 Gy to the prostate and proximal seminal vesicles and 25 Gy to the lymph nodes delivered over 5 weekly fractions using image guidance with cone beam computed tomography. Mean rectal DVH values at 5-Gy intervals and mean DVH curves were compared between patients with rectal bleeding (B) versus no bleeding (NB).

Results: There were 12 B and 33 NB patients in the pooled group. Rectal bleeding was more frequent and of higher grade among FASTR patients (8/15, 5 grade 2 or higher) than among SATURN patients (4/30, all grade 1). For any bleeding (grade ≥1), individual dose-volume points in the 20 to 40 Gy range were significantly different (2-sided P < .05) between the B and NB groups, with the 40 Gy point being the most significant (B: V40 = 1.53%, standard deviation (SD), 1.32; NB: V40 = 0.69%, SD, 1.46; P = .006). For grade ≥2 bleeding, the V20 Gy was most significant (B: 68.4%, SD, 4.76; NB: 40.45%, SD, 13.9; P < .001).

Conclusions: The higher relative dose volumes to the rectum (V20-V40) were most strongly associated with clinically significant bleeding in this analysis and are consistent with findings of series that used H-SIB to treat prostate only. Differences in the prostate target volumes and planning margins likely account for the differences in the rates and grades of rectal bleeding observed between trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.prro.2017.06.002DOI Listing
July 2018

Stereotactic ablative radiotherapy in the treatment of low and intermediate risk prostate cancer: Is there an optimal dose?

Radiother Oncol 2017 06 19;123(3):478-482. Epub 2017 Apr 19.

Odette Cancer Centre, Sunnybrook Health Sciences Centre, Canada; Department of Radiation Oncology, University of Toronto, Canada; Institute of Health Policy, Measurement and Evaluation, University of Toronto, Canada. Electronic address:

Purpose: To investigate if stereotactic ablative radiotherapy (SABR) dose is associated with PSA at 3years (PSA) in the treatment of localized prostate cancer and to explore predictors of late genitourinary (GU) toxicity.

Materials And Methods: Three prospective trials of SABR were undertaken at our institution: 1) 35Gy/5 fractions/29days; 2) 40Gy/5 fractions/29days; 3) 40Gy/5 fractions/11 or 29days. PSA was analyzed as a continuous variable. Toxicity was defined as the worst new toxicity and assessed using the radiation therapy oncology group (RTOG) late morbidity scheme. Univariate and multivariable regression analyses were conducted to assess the association between dose and PSA, and to explore predictors of late grade 2+ GU toxicity.

Results: Median PSA3y was 0.64 (intraquartile range (IQR): 0.41-1.12) and 0.27 (IQR: 0.12-0.55) ng/mL for patients treated with 35 and 40Gy respectively. A dose of 40Gy was an independent predictor of lower PSA on multivariable analysis (p<0.001). Dose of 40Gy (odds ratio (OR): 16.69, 95%CI: 5.78, 48.20, p<0.001) and higher International Prostate Symptom Score (OR: 1.01, 95%CI: 1.04, 1.16, p=0.001) predicted for late grade 2+ GU toxicity on multivariable logistic regression.

Conclusions: This analysis suggests that higher SABR dose is associated with lower PSA. Strategies to allow safe SABR dose escalation should be further investigated.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.radonc.2017.03.006DOI Listing
June 2017

Predictive Parameters of Symptomatic Hematochezia Following 5-Fraction Gantry-Based SABR in Prostate Cancer.

Int J Radiat Oncol Biol Phys 2016 Apr 23;94(5):1043-51. Epub 2015 Dec 23.

Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada; Department of Health Policy, Measurement and Evaluation, University of Toronto, Toronto, Ontario, Canada. Electronic address:

Purpose: This study identified predictors of high-grade late hematochezia (HH) following 5-fraction gantry-based stereotactic ablative radiation therapy (SABR).

Methods And Materials: Hematochezia data for 258 patients who received 35 to 40 Gy SABR in 5-fractions as part of sequential phase 2 prospective trials was retrieved. Grade 2 or higher late rectal bleeding was labeled HH. Hematochezia needing steroid suppositories, 4% formalin, or 1 to 2 sessions of argon plasma coagulation (APC) was labeled grade 2. More than 2 sessions of APC, blood transfusion, or a course of hyperbaric oxygen was grade 3 and development of visceral fistula, grade 4. Various dosimetric and clinical factors were analyzed using univariate and multivariate analyses. Receiver operating characteristic (ROC) curve analysis and recursive partitioning analysis were used to determine clinically valid cut-off points and identify risk groups, respectively.

Results: HH was observed in 19.4%, grade ≥3 toxicity in 3.1%. Median follow-up was 29.7 months (interquartile range [IQR]: 20.6-61.7) Median time to develop HH was 11.7 months (IQR: 9.0-15.2) from the start of radiation. At 2 years, cumulative HH was 4.9%, 27.2%, and 42.1% in patients who received 35 Gy to prostate (4-mm planning target volume [PTV] margin), 40 Gy to prostate (5-mm PTV margin), and 40 Gy to prostate/seminal vesicles (5-mm PTV margin), respectively (P<.0001). In the ROC analysis, volume of rectum receiving radiation dose of 38 Gy (V38) was a strong predictor of HH with an area under the curve of 0.65. In multivariate analysis, rectal V38 (≥2.0 cm(3); odds ratio [OR]: 4.7); use of anticoagulants in the follow-up period (OR: 6.5) and presence of hemorrhoids (OR: 2.7) were the strongest predictors. Recursive partitioning analysis showed rectal V38 < 2.0 cm(3), and use of anticoagulants or rectal V38 ≥ 2.0 cm(3) plus 1 other risk factor resulted in an HH risk of >30%.

Conclusions: Rectal V38 and 2 clinical factors were strong predictors of HH following 5-fraction SABR. Planning constraints should keep rectal V38 below 2.0 cm(3).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijrobp.2015.12.010DOI Listing
April 2016

Dose-escalation of five-fraction SABR in prostate cancer: Toxicity comparison of two prospective trials.

Radiother Oncol 2016 Jan 12;118(1):112-7. Epub 2016 Jan 12.

Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Canada; Department of Radiation Oncology, University of Toronto, Canada; Institute of Health Policy, Measurement and Evaluation, University of Toronto, Canada. Electronic address:

Purpose: To compare biochemical outcome and toxicities of two prospective 5-fraction stereotactic ablative radiotherapy (SABR) studies in prostate cancer.

Materials And Methods: 84 patients in pHART3 received 35 Gy, 30 patients in pHART6 received 40 Gy in 5-fractions to the prostate alone, once weekly. 4mm and 5mm PTV margins were used, respectively. Biochemical outcome, acute, late and cumulative genitourinary (GU)/gastrointestinal (GI) toxicities were compared.

Results: Median follow-up was 74 and 36 months, respectively. Median prostate specific antigen nadir was 0.4 ng/ml and 0.3 ng/ml. 2-, 4- and 6-year biochemical relapse-free survival (bRFS-2+nadir) was 100%, 98.7% and 95.9% in pHART3; 100%, 100% and not reached in pHART6 (p=0.91). There was one acute grade 3 GU (retention) and late grade 4 GI (fistula) toxicity in pHART3, none in pHART6. One patient in each study had persisting grade 2+ toxicity at the last follow-up. pHART6 patients had a greater grade 2+ cumulative GU (5% versus 24.2%) and GI (7.6% versus 26.2%) toxicities.

Conclusions: Patients receiving dose-escalated SABR had slightly lower PSA nadir and similar bRFS, longer follow-up is needed to better estimate biochemical outcomes. There was a greater risk of grade 2 toxicity in pHART6 but not grade 3+ toxicities. Persisting toxicity at the last follow-up is similar.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.radonc.2015.12.020DOI Listing
January 2016

Clinical evaluation of an endorectal immobilization system for use in prostate hypofractionated Stereotactic Ablative Body Radiotherapy (SABR).

Radiat Oncol 2015 May 30;10:122. Epub 2015 May 30.

Department of Medical Physics, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.

Background: The objective of this study was to evaluate a novel prostate endorectal immobilization system (EIS) for improving the delivery of hypofractionated Stereotactic Ablative Body Radiotherapy (SABR) for prostate cancer.

Methods: Twenty patients (n = 20) with low- or intermediate-risk prostate cancer (T1-T2b, Gleason Score < 7, PSA ≤ 20 ng/mL), were treated with an EIS in place using Volumetric Modulated Arc Therapy (VMAT), to a prescription dose of 26 Gy delivered in 2 fractions once per week; the intent of the institutional clinical trial was an attempt to replicate brachytherapy-like dosimetry using SABR. EBT3 radiochromic film embedded within the EIS was used as a quality assurance measure of the delivered dose; additionally, prostate intrafraction motion captured using pre- and post-treatment conebeam computed tomography (CBCT) scans was evaluated. Treatment plans were generated for patients with- and without the EIS to evaluate its effects on target and rectal dosimetry.

Results: None of the observed 3-dimensional prostate displacements were ≥ 3 mm over the elapsed treatment time. A Gamma passing rate of 95.64 ± 4.28 % was observed between planned and delivered dose profiles on EBT3 film analysis in the low-dose region. No statistically significant differences between treatment plans with- and without-EIS were observed for rectal, bladder, clinical target volume (CTV), and PTV contours (p = 0.477, 0.484, 0.487, and 0.487, respectively). A mean rectal V80% of 1.07 cc was achieved for plans using the EIS.

Conclusions: The EIS enables the safe delivery of brachytherapy-like SABR plans to the prostate while having minimal impact on treatment planning and rectal dosimetry. Consistent and reproducible immobilization of the prostate is possible throughout the duration of these treatments using such a device.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13014-015-0426-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4456701PMC
May 2015

Full-thickness closure in breast-conserving surgery: the impact on radiotherapy target definition for boost and partial breast irradiation. A multimodality image evaluation.

Ann Surg Oncol 2014 Nov 30;21(12):3774-9. Epub 2014 May 30.

Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, The Netherlands,

Background: During breast-conserving surgery (BCS), surgeons increasingly perform full-thickness closure (FTC) to prevent seroma formation. This could potentially impair precision of target definition for boost and accelerated partial breast irradiation (APBI). The purpose of this study was to investigate the precision of target volume definition following BCS with FTC among radiation oncologists, using various imaging modalities.

Methods: Twenty clinical T1-2N0 patients, scheduled for BCS involving clip placement and FTC, were included in the study. Seven experienced breast radiation oncologists contoured the tumor bed on computed tomography (CT), magnetic resonance imaging (MRI) and fused CT-MRI datasets. A total of 361 observer pairs per image modality were analyzed. A pairwise conformity among the generated contours of the observers and the distance between their centers of mass (dCOM) were calculated.

Results: On CT, median conformity was 44 % [interquartile range (IQR) 28-58 %] and median dCOM was 6 mm (IQR 3-9 mm). None of the outcome measures improved when MRI or fused CT-MRI were used. In two patients, superficial closure was performed instead of FTC. In these 14 image sets and 42 observer pairs, median conformity increased to 70 %.

Conclusions: Localization of the radiotherapy target after FTC is imprecise, on both CT and MRI. This could potentially lead to a geographical miss in patients at increased risk of local recurrence receiving a radiation boost, or for those receiving APBI. These findings highlight the importance for breast surgeons to clearly demarcate the tumor bed when performing FTC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1245/s10434-014-3801-8DOI Listing
November 2014
-->