Robin Kalisvaart

A Multi-institutional Clinical Trial of Rectal Dose Reduction via Injected Polyethylene-Glycol Hydrogel During Intensity Modulated Radiation Therapy for Prostate Cancer: Analysis of Dosimetric Outcomes

PURPOSE To characterize the effect of a prostate-rectum spacer on dose to rectum during external beam radiation therapy for prostate cancer and to assess for factors correlated with rectal dose reduction. METHODS AND MATERIALS Fifty-two patients at 4 institutions were enrolled into a prospective pilot clinical trial. Patients underwent baseline scans and then were injected with perirectal spacing hydrogel and rescanned. Intensity modulated radiation therapy plans were created on both scans for comparison. The objectives were to establish rates of creation of ≥ 7.5 mm of prostate-rectal separation, and decrease in rectal V70 of ≥ 25%. Multiple regression analysis was performed to evaluate the associations between preinjection and postinjection changes in rectal V70 and changes in plan conformity, rectal volume, bladder volume, bladder V70, planning target volume (PTV), and postinjection midgland separation, gel volume, gel thickness, length of PTV/gel contact, and gel left-to-right symmetry. RESULTS Hydrogel resulted in ≥7.5-mm prostate-rectal separation in 95.8% of patients; 95.7% had decreased rectal V70 of ≥ 25%, with a mean reduction of 8.0 Gy. There were no significant differences in preinjection and postinjection prostate, PTV, rectal, and bladder volumes. Plan conformities were significantly different before versus after injection (P=.02); plans with worse conformity indexes after injection compared with before injection (n=13) still had improvements in rectal V70. In multiple regression analysis, greater postinjection reduction in V70 was associated with decreased relative postinjection plan conformity (P=.01). Reductions in V70 did not significantly vary by institution, despite significant interinstitutional variations in plan conformity. There were no significant relationships between reduction in V70 and the other characteristics analyzed. CONCLUSIONS Injection of hydrogel into the prostate-rectal interface resulted in dose reductions to rectum for >90% of patients treated. Rectal sparing was statistically significant across a range of 10 to 75 Gy and was demonstrated within the presence of significant interinstitutional variability in plan conformity, target definitions, and injection results.

Absorbable hydrogel spacer use in men undergoing prostate cancer radiotherapy: 12 month toxicity and proctoscopy results of a prospective multicenter phase II trial

BackgroundRadiation therapy is one of the recommended treatment options for localized prostate cancer. In randomized trials, dose escalation was correlated with better biochemical control but also with higher rectal toxicity. A prospective multicenter phase II study was carried out to evaluate the safety, clinical and dosimetric effects of the hydrogel prostate-rectum spacer. Here we present the 12 months toxicity results of this trial.MethodsFifty two patients with localized prostate cancer received a transperineal PEG hydrogel injection between the prostate and rectum, and then received IMRT to a dose of 78 Gy. Gastrointestinal and genitourinary toxicity were recorded during treatment and at 3, 6 and 12 months following irradiation by using the RTOG/EORTC criteria. Additionally, proctoscopy was performed 12 months after treatment and the results were scored using the Vienna Rectoscopy Scale (VRS).ResultsOf the patients treated 39.6% and 12.5% experienced acute Grade 1 and Grade 2 GI toxicity, respectively. There was no Grade 3 or Grade 4 acute GI toxicity experienced in the study. Only 4.3% showed late Grade 1 GI toxicity, and there was no late Grade 2 or greater GI toxicity experienced in the study. A total of 41.7%, 35.4% and 2.1% of the men experienced acute Grade 1, Grade 2 and Grade 3 GU toxicity, respectively. There was no Grade 4 acute GU toxicity experienced in the study. Late Grade 1 and Grade 2 GU toxicity was experienced in 17.0% and 2.1% of the patients, respectively. There was no late Grade 3 or greater GU toxicity experienced in the study. Seventy one percent of the patients had a VRS score of 0, and one patient (2%) had Grade 3 teleangiectasia. There was no evidence of ulceration, stricture or necrosis at 12 months.ConclusionThe use of PEG spacer gel is a safe and effective method to spare the rectum from higher dose and toxicity.

Prostate tumor delineation using multiparametric magnetic resonance imaging: Inter-observer variability and pathology validation

BACKGROUND AND PURPOSE Boosting the dose to the largest (dominant) lesion in radiotherapy of prostate cancer may improve treatment outcome. The success of this approach relies on the detection and delineation of tumors. The agreement among teams of radiation oncologists and radiologists delineating lesions on multiparametric magnetic resonance imaging (mp-MRI) was assessed by measuring the distances between observer contours. The accuracy of detection and delineation was determined using whole-mount histopathology specimens as reference. MATERIAL AND METHODS Six observer teams delineated tumors on mp-MRI of 20 prostate cancer patients who underwent a prostatectomy. To assess the inter-observer agreement, the inter-observer standard deviation (SD) of the contours was calculated for tumor sites which were identified by all teams. RESULTS Eighteen of 89 lesions were identified by all teams, all were dominant lesions. The median histological volume of these was 2.4cm(3). The median inter-observer SD of the delineations was 0.23cm. Sixty-six of 69 satellites were missed by all teams. CONCLUSION Since all teams identify most dominant lesions, dose escalation to the dominant lesion is feasible. Sufficient dose to the whole prostate may need to be maintained to prevent under treatment of smaller lesions and undetected parts of larger lesions.

Impact of tumour invasion on seminal vesicles mobility in radiotherapy of prostate cancer

PURPOSE Mobility of the seminal vesicles relative to the prostate challenges adequate dose coverage. The aim of this study was to assess the impact of tumour invasion on SV mobility. METHODS AND MATERIALS Three groups of 30 prostate cancer patients with (1) no invasion on MR, (2) minimal invasion (<5mm), and (3) extensive invasion (>5mm) were studied. Translations and rotations of the SV were measured with CBCT and compared between the three groups. RESULTS In the extensive group the random SV translations were significantly lower in comparison with the no invasion group in the LR: 0.15 vs 0.16 cm (p=0.015), CC: 0.17 vs 0.23 cm (p=0.004) and AP direction: 0.19 vs 0.26 cm (p=0.002). Also the random SV rotation on the LR axis was significantly lower: 5.2 vs 6.3° (p=0.035). In comparison with the minimal invasion group the random SV translations were significantly lower in the extensive group in the CC: 0.17 vs 0.24 cm (p=0.001) and AP direction 0.19 vs 0.31 cm (p=0.007) and for the rotation on the LR axis: 5.2 vs 6.5° (p=0.043). CONCLUSION Increasing tumour invasion in the SV reduces the mobility of the SV, however the mobility remains considerable.

OC-0078: Impact of tumor invasion on seminal vesicles mobility in radiotherapy of T3b prostate cancer

adjacent structures. For these patients a mask was created from the GTV by a 2cm expansion after which the GTV itself was removed (figure C,D), effectively registering the adjacent structures. This method was evaluated on five weekly fractions of 24 patients. The second method was applied on patients with a non-attached tumor. In this method the local rigid registration was expanded by a scaling factor such that the regressing tumor in the CBCT was magnified to the original size of the tumor of the reference CT-scan during the registration (figure G,H). This method was applied on 5 patients and also five weekly fractions were evaluated. Bland-Altman analysis was applied to quantify the limits of agreement between these registration methods and the clinically approved registrations. All automatic registrations were visually validated to assess the success rate. Results: The limits of agreement between the registration method for regressing tumors attached to surrounding structures showed limits of agreement with the clinical method of -2.6—2.9mm for the LR direction, -2.9—2.8mm for the CC direction and -3.1—3.2mm for the AP direction. The alignment differences between these two methods were 1.3 (LR), 1.4 (CC) and 1.4 mm (AP) systematically and 1.0, 1.1 and 1.2mm randomly. This automatic method had a success rate of 91%. The limits of agreement between the registration method for non-attached tumors and the clinical method were larger with -6.0—4.1mm (LR), -8.5—7.1mm (CC) and -3.3—4.3mm (AP). The alignment differences between these two methods were 4.0 (LR), 3.9 (CC) and 3.6mm (AP) systematically and 4.0, 3.3 and 2.4mm randomly. The success rate of these automatic registrations was 100%. Conclusions: The registration method developed for regressing tumors attached to surrounding structures proved to be a reliable method for automatic tumor registration. The registration method for regressing non-attached tumors is promising but needs further investigation on a larger patient cohort.

A multi-institutional clinical trial of rectal dose reduction via injected polyethylene-glycol hydrogel during IMRT for prostate cancer: Analysis of dosimetric outcomes.

35 Background: To characterize the effect of a prostate-rectum spacer on dose to rectum during external beam radiotherapy for prostate cancer, and to assess for factors correlated with rectal dose reduction. METHODS Fifty-two patients at 4 institutions were enrolled onto a prospective pilot clinical trial. Patients underwent baseline scans, then were injected with perirectal spacing hydrogel and re-scanned. IMRT plans were created on both scans for comparison. Objectives were to establish rates of creation of ≥7.5mm of prostate-rectal separation, and decrease in rectal V70 of ≥25%. Multiple regression analysis was performed to evaluate associations between pre- vs. post-injection changes in rectal V70 and changes in plan conformity, rectal volume, bladder volume, bladder V70, PTV volume, as well as post-injection mid-gland separation, gel volume, gel thickness, length of PTV/gel contact, or gel left-to-right symmetry. RESULTS Hydrogel resulted in > 7.5mm prostate-rectal separation in 95.8% of patients; 95.7% had decreased rectal V70 of > 25%, with mean reduction of 8.0 Gy. There were no significant differences in pre- and post-injection prostate, PTV, rectal, and bladder volumes. Plan conformities were significantly different pre- vs. post-injection (P = 0.02). In multiple regression analysis, change in plan conformity was negatively associated with reduction in V70 (P=0.01); plans with worse conformity indexes post-injection compared to pre-injection (n=13) still had improvements in rectal V70. Reductions in V70 did not significantly vary by institution, despite significant inter-institutional variations in plan conformity. There were no significant relationships between reduction in V70 and the other characteristics analyzed. CONCLUSIONS Injection of hydrogel into prostate-rectal interface resulted in dose reductions to rectum for > 90% of patients treated. Rectal sparing was statistically significant across a range of 10-75 Gy, and was demonstrated within the presence of significant inter-institutional variability in plan conformity, target definitions, and injection results.

A multi-institutional clinical trial of rectal dose reduction via injected polyethylene-glycol hydrogel during intensity modulated radiation therapy for prostate cancer

PURPOSE To characterize the effect of a prostate-rectum spacer on dose to rectum during external beam radiation therapy for prostate cancer and to assess for factors correlated with rectal dose reduction. METHODS AND MATERIALS Fifty-two patients at 4 institutions were enrolled into a prospective pilot clinical trial. Patients underwent baseline scans and then were injected with perirectal spacing hydrogel and rescanned. Intensity modulated radiation therapy plans were created on both scans for comparison. The objectives were to establish rates of creation of ≥ 7.5 mm of prostate-rectal separation, and decrease in rectal V70 of ≥ 25%. Multiple regression analysis was performed to evaluate the associations between preinjection and postinjection changes in rectal V70 and changes in plan conformity, rectal volume, bladder volume, bladder V70, planning target volume (PTV), and postinjection midgland separation, gel volume, gel thickness, length of PTV/gel contact, and gel left-to-right symmetry. RESULTS Hydrogel resulted in ≥7.5-mm prostate-rectal separation in 95.8% of patients; 95.7% had decreased rectal V70 of ≥ 25%, with a mean reduction of 8.0 Gy. There were no significant differences in preinjection and postinjection prostate, PTV, rectal, and bladder volumes. Plan conformities were significantly different before versus after injection (P=.02); plans with worse conformity indexes after injection compared with before injection (n=13) still had improvements in rectal V70. In multiple regression analysis, greater postinjection reduction in V70 was associated with decreased relative postinjection plan conformity (P=.01). Reductions in V70 did not significantly vary by institution, despite significant interinstitutional variations in plan conformity. There were no significant relationships between reduction in V70 and the other characteristics analyzed. CONCLUSIONS Injection of hydrogel into the prostate-rectal interface resulted in dose reductions to rectum for >90% of patients treated. Rectal sparing was statistically significant across a range of 10 to 75 Gy and was demonstrated within the presence of significant interinstitutional variability in plan conformity, target definitions, and injection results.

A multi-institutional clinical trial of rectal dose reduction via injected polyethylene-glycol hydrogel during IMRT for prostate cancer: Analysis of dosimetric outcomes

PURPOSE To characterize the effect of a prostate-rectum spacer on dose to rectum during external beam radiation therapy for prostate cancer and to assess for factors correlated with rectal dose reduction. METHODS AND MATERIALS Fifty-two patients at 4 institutions were enrolled into a prospective pilot clinical trial. Patients underwent baseline scans and then were injected with perirectal spacing hydrogel and rescanned. Intensity modulated radiation therapy plans were created on both scans for comparison. The objectives were to establish rates of creation of ≥ 7.5 mm of prostate-rectal separation, and decrease in rectal V70 of ≥ 25%. Multiple regression analysis was performed to evaluate the associations between preinjection and postinjection changes in rectal V70 and changes in plan conformity, rectal volume, bladder volume, bladder V70, planning target volume (PTV), and postinjection midgland separation, gel volume, gel thickness, length of PTV/gel contact, and gel left-to-right symmetry. RESULTS Hydrogel resulted in ≥7.5-mm prostate-rectal separation in 95.8% of patients; 95.7% had decreased rectal V70 of ≥ 25%, with a mean reduction of 8.0 Gy. There were no significant differences in preinjection and postinjection prostate, PTV, rectal, and bladder volumes. Plan conformities were significantly different before versus after injection (P=.02); plans with worse conformity indexes after injection compared with before injection (n=13) still had improvements in rectal V70. In multiple regression analysis, greater postinjection reduction in V70 was associated with decreased relative postinjection plan conformity (P=.01). Reductions in V70 did not significantly vary by institution, despite significant interinstitutional variations in plan conformity. There were no significant relationships between reduction in V70 and the other characteristics analyzed. CONCLUSIONS Injection of hydrogel into the prostate-rectal interface resulted in dose reductions to rectum for >90% of patients treated. Rectal sparing was statistically significant across a range of 10 to 75 Gy and was demonstrated within the presence of significant interinstitutional variability in plan conformity, target definitions, and injection results.