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

Uhl M, Herfarth K, Eble MJ, Pinkawa M, van Triest B, Kalisvaart R, Weber DC, Miralbell R, Song DY, DeWeese TL - Radiat Oncol (2014)

Bottom Line: Additionally, proctoscopy was performed 12 months after treatment and the results were scored using the Vienna Rectoscopy Scale (VRS).There was no evidence of ulceration, stricture or necrosis at 12 months.The use of PEG spacer gel is a safe and effective method to spare the rectum from higher dose and toxicity.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Radiation Oncology, University of Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany. Matthias.Uhl@med.uni-heidelberg.de.

ABSTRACT

Background: Radiation 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.

Methods: Fifty 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).

Results: Of 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.

Conclusion: The use of PEG spacer gel is a safe and effective method to spare the rectum from higher dose and toxicity.

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Related in: MedlinePlus

Comparison of gastrointestinal toxicity ≥ Grade 2 with other trials. Lips et al.[18]: PTV = Prostate + seminal vesicles + 8 mm margin, 76 Gy mean dose, not more than 5% of rectum received ≥ 72 Gy. Vora et al.[19]: PTV = Prostate + seminal vesicles + 6-10 mm margin, 50.4 Gy + Boost (median 75.6 Gy), not more than 40%/30%/10% of Rectum received ≥ 65 Gy/70 Gy/75 Gy, not more than 1.8 cm2 of rectum received 81 Gy. Zietman et al.[8]: PTV = Prostate + seminal vesicles + 10 mm margin for Photontherapy (50.4 Gy) and 5mm margin for proton Boost (28.8 GyE).
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Figure 2: Comparison of gastrointestinal toxicity ≥ Grade 2 with other trials. Lips et al.[18]: PTV = Prostate + seminal vesicles + 8 mm margin, 76 Gy mean dose, not more than 5% of rectum received ≥ 72 Gy. Vora et al.[19]: PTV = Prostate + seminal vesicles + 6-10 mm margin, 50.4 Gy + Boost (median 75.6 Gy), not more than 40%/30%/10% of Rectum received ≥ 65 Gy/70 Gy/75 Gy, not more than 1.8 cm2 of rectum received 81 Gy. Zietman et al.[8]: PTV = Prostate + seminal vesicles + 10 mm margin for Photontherapy (50.4 Gy) and 5mm margin for proton Boost (28.8 GyE).

Mentions: While studies have demonstrated that dose escalation improves local control in men with prostate cancer, concerns of rectal toxicity limits implementation[6,8]. Thus, a meaningful dose escalation is only possible with a better sparing of rectal tissue. Conformal techniques such as brachytherapy, IMRT and proton therapy are helping to resolve this problem. Despite improvements in dose conformity, intra-fraction prostate motion can move the anterior rectum into the high dose region. A reduction of the irradiated volume posterior to the prostate is not a good solution, since most prostate cancers in the peripheral zone of the gland, occur adjacent to the rectum. A very simple and logical solution is to create more distance between the required volume to be irradiated and the anterior portion of the prostate. This can be easily achieved with the injection of a spacer between the rectum and prostate to create and maintain space throughout treatment. The feasibility and effectiveness of the hydrogel injection were objectives of this study. It has already been demonstrated that the injection procedure is safe and a stable 1 cm distance between the prostate and the rectum can be generated[15] resulting in a significant dose reduction to the rectum[13]. The prospectively collected data show a very low GI acute toxicity with only 12.5% Grade 2, and no Grade 3 or higher toxicity. A total of 95.7% of patients had no late GI toxicity and only 4.3% (n = 2) had late Grade 1 GI toxicity. After completion of the follow up time, these results validate our published data with early results[14]. Despite some differences in margins and dose delivered, the lower GI toxicity rates in this study are remarkable when compared to other studies (Figure 2)[8,18,19]. Like a number of other toxicity reports, proctoscopy was also performed 12 months after the end of therapy[17]. Ippolito et al. could show that early proctoscopy 12 months after irradiation can be used as a surrogate endpoint for late rectal toxicity. The incidence of late rectal toxicity ≥ grade 2 was higher in patients with VRS score grade ≥2 or 3[20]. In our results no evidence of ulceration, stricture or necrosis was found. Seventy one percent of patients had a VRS score 0, with 13% and 2% having Grade 2 and Grade 3, respectively. Another prospective multicenter trial demonstrated a direct correlation between VRS and EORTC/RTOG score 12 months after prostate irradiation with 70 or 74 Gy[21]. At 12 months following IMRT the pathological changes to rectum mucosa in this hydrogel spacer trial are less that in the Goldner et al. prospective trial, despite the higher radiation dose in this hydrogel spacer study (Figure 3). Other studies with spacer between the rectum and prostate show similar toxicity reductions. Noyes et al. evaluated human collagen injections into the perirectal space and found a subsequent reduction of GI toxicity in patients compared with a historical control group[10]. Wilder published similar results after hyaluronic acid injection[12]. The PEG gel in our study was stable during treatment and was reabsorbed within a year. The patients in this hydrogel trial experienced 41.7%/35.4%/2.1% Grade 1/2/3 acute GU toxicity, respectively. A total of 35% and 2% had Grade 1 and Grade 2 GU toxicity at 12 months after treatment. No ≥ Grade 3 GU toxicity was experienced in this trial. Thus, the rate of patients with GU toxicity ≥ 2 is favorable compared to studies without spacers[8,18,19]. Despite the added cost of the product, routine incorporation of hydrogel may result in significant overall health system savings as a result of decreased toxicity and less frequent need for proctitis treatment, fewer treatment fractions (hypofractionation) may be made even more safe and, potentially, a lower rate of cancer recurrence (dose escalation).


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

Uhl M, Herfarth K, Eble MJ, Pinkawa M, van Triest B, Kalisvaart R, Weber DC, Miralbell R, Song DY, DeWeese TL - Radiat Oncol (2014)

Comparison of gastrointestinal toxicity ≥ Grade 2 with other trials. Lips et al.[18]: PTV = Prostate + seminal vesicles + 8 mm margin, 76 Gy mean dose, not more than 5% of rectum received ≥ 72 Gy. Vora et al.[19]: PTV = Prostate + seminal vesicles + 6-10 mm margin, 50.4 Gy + Boost (median 75.6 Gy), not more than 40%/30%/10% of Rectum received ≥ 65 Gy/70 Gy/75 Gy, not more than 1.8 cm2 of rectum received 81 Gy. Zietman et al.[8]: PTV = Prostate + seminal vesicles + 10 mm margin for Photontherapy (50.4 Gy) and 5mm margin for proton Boost (28.8 GyE).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4016630&req=5

Figure 2: Comparison of gastrointestinal toxicity ≥ Grade 2 with other trials. Lips et al.[18]: PTV = Prostate + seminal vesicles + 8 mm margin, 76 Gy mean dose, not more than 5% of rectum received ≥ 72 Gy. Vora et al.[19]: PTV = Prostate + seminal vesicles + 6-10 mm margin, 50.4 Gy + Boost (median 75.6 Gy), not more than 40%/30%/10% of Rectum received ≥ 65 Gy/70 Gy/75 Gy, not more than 1.8 cm2 of rectum received 81 Gy. Zietman et al.[8]: PTV = Prostate + seminal vesicles + 10 mm margin for Photontherapy (50.4 Gy) and 5mm margin for proton Boost (28.8 GyE).
Mentions: While studies have demonstrated that dose escalation improves local control in men with prostate cancer, concerns of rectal toxicity limits implementation[6,8]. Thus, a meaningful dose escalation is only possible with a better sparing of rectal tissue. Conformal techniques such as brachytherapy, IMRT and proton therapy are helping to resolve this problem. Despite improvements in dose conformity, intra-fraction prostate motion can move the anterior rectum into the high dose region. A reduction of the irradiated volume posterior to the prostate is not a good solution, since most prostate cancers in the peripheral zone of the gland, occur adjacent to the rectum. A very simple and logical solution is to create more distance between the required volume to be irradiated and the anterior portion of the prostate. This can be easily achieved with the injection of a spacer between the rectum and prostate to create and maintain space throughout treatment. The feasibility and effectiveness of the hydrogel injection were objectives of this study. It has already been demonstrated that the injection procedure is safe and a stable 1 cm distance between the prostate and the rectum can be generated[15] resulting in a significant dose reduction to the rectum[13]. The prospectively collected data show a very low GI acute toxicity with only 12.5% Grade 2, and no Grade 3 or higher toxicity. A total of 95.7% of patients had no late GI toxicity and only 4.3% (n = 2) had late Grade 1 GI toxicity. After completion of the follow up time, these results validate our published data with early results[14]. Despite some differences in margins and dose delivered, the lower GI toxicity rates in this study are remarkable when compared to other studies (Figure 2)[8,18,19]. Like a number of other toxicity reports, proctoscopy was also performed 12 months after the end of therapy[17]. Ippolito et al. could show that early proctoscopy 12 months after irradiation can be used as a surrogate endpoint for late rectal toxicity. The incidence of late rectal toxicity ≥ grade 2 was higher in patients with VRS score grade ≥2 or 3[20]. In our results no evidence of ulceration, stricture or necrosis was found. Seventy one percent of patients had a VRS score 0, with 13% and 2% having Grade 2 and Grade 3, respectively. Another prospective multicenter trial demonstrated a direct correlation between VRS and EORTC/RTOG score 12 months after prostate irradiation with 70 or 74 Gy[21]. At 12 months following IMRT the pathological changes to rectum mucosa in this hydrogel spacer trial are less that in the Goldner et al. prospective trial, despite the higher radiation dose in this hydrogel spacer study (Figure 3). Other studies with spacer between the rectum and prostate show similar toxicity reductions. Noyes et al. evaluated human collagen injections into the perirectal space and found a subsequent reduction of GI toxicity in patients compared with a historical control group[10]. Wilder published similar results after hyaluronic acid injection[12]. The PEG gel in our study was stable during treatment and was reabsorbed within a year. The patients in this hydrogel trial experienced 41.7%/35.4%/2.1% Grade 1/2/3 acute GU toxicity, respectively. A total of 35% and 2% had Grade 1 and Grade 2 GU toxicity at 12 months after treatment. No ≥ Grade 3 GU toxicity was experienced in this trial. Thus, the rate of patients with GU toxicity ≥ 2 is favorable compared to studies without spacers[8,18,19]. Despite the added cost of the product, routine incorporation of hydrogel may result in significant overall health system savings as a result of decreased toxicity and less frequent need for proctitis treatment, fewer treatment fractions (hypofractionation) may be made even more safe and, potentially, a lower rate of cancer recurrence (dose escalation).

Bottom Line: Additionally, proctoscopy was performed 12 months after treatment and the results were scored using the Vienna Rectoscopy Scale (VRS).There was no evidence of ulceration, stricture or necrosis at 12 months.The use of PEG spacer gel is a safe and effective method to spare the rectum from higher dose and toxicity.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Radiation Oncology, University of Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany. Matthias.Uhl@med.uni-heidelberg.de.

ABSTRACT

Background: Radiation 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.

Methods: Fifty 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).

Results: Of 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.

Conclusion: The use of PEG spacer gel is a safe and effective method to spare the rectum from higher dose and toxicity.

Show MeSH
Related in: MedlinePlus