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Hyaluronic acid spacer in prostate cancer radiotherapy: dosimetric effects, spacer stability and long-term toxicity and PRO in a phase II study
Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.ORCID iD: 0000-0003-4132-6915
Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
Umeå University, Faculty of Medicine, Department of Nursing.ORCID iD: 0000-0002-1248-5581
Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.ORCID iD: 0000-0002-3683-3763
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2023 (English)In: Radiation Oncology, E-ISSN 1748-717X, Vol. 18, no 1, article id 1Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Perirectal spacers may be beneficial to reduce rectal side effects from radiotherapy (RT). Here, we present the impact of a hyaluronic acid (HA) perirectal spacer on rectal dose as well as spacer stability, long-term gastrointestinal (GI) and genitourinary (GU) toxicity and patient-reported outcome (PRO).

METHODS: In this phase II study 81 patients with low- and intermediate-risk prostate cancer received transrectal injections with HA before external beam RT (78 Gy in 39 fractions). The HA spacer was evaluated with MRI four times; before (MR0) and after HA-injection (MR1), at the middle (MR2) and at the end (MR3) of RT. GI and GU toxicity was assessed by physician for up to five years according to the RTOG scale. PROs were collected using the Swedish National Prostate Cancer Registry and Prostate cancer symptom scale questionnaires.

RESULTS: There was a significant reduction in rectal V70% (54.6 Gy) and V90% (70.2 Gy) between MR0 and MR1, as well as between MR0 to MR2 and MR3. From MR1 to MR2/MR3, HA thickness decreased with 28%/32% and CTV-rectum space with 19%/17% in the middle level. The cumulative late grade ≥ 2 GI toxicity at 5 years was 5% and the proportion of PRO moderate or severe overall bowel problems at 5 years follow-up was 12%. Cumulative late grade ≥ 2 GU toxicity at 5 years was 12% and moderate or severe overall urinary problems at 5 years were 10%.

CONCLUSION: We show that the HA spacer reduced rectal dose and long-term toxicity.

Place, publisher, year, edition, pages
BioMed Central (BMC), 2023. Vol. 18, no 1, article id 1
Keywords [en]
Hyaluronic Acid, Prostate cancer, Radiotherapy, Rectal toxicity
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:umu:diva-203799DOI: 10.1186/s13014-022-02197-xISI: 000906713000001PubMedID: 36593460Scopus ID: 2-s2.0-85145492354OAI: oai:DiVA.org:umu-203799DiVA, id: diva2:1729324
Funder
Region VästernorrlandCancerforskningsfonden i NorrlandVisare NorrAvailable from: 2023-01-20 Created: 2023-01-20 Last updated: 2024-07-04Bibliographically approved
In thesis
1. MRI in prostate cancer: implications for target volume
Open this publication in new window or tab >>MRI in prostate cancer: implications for target volume
2023 (English)Doctoral thesis, comprehensive summary (Other academic)
Alternative title[sv]
MRT bildtagning vid prostatacancer : implikationer för strålbehandlingsområdet?
Abstract [en]

Prostate cancer (PCa) is the most common cancer among men, with 10 000 new cases per year in Sweden [1]. To diagnose PCa, magnetic resonance imaging (MRI) is used to identify and classify the disease. The patient’s treatment strategy depends on PCa classification and clinical data, which are weighted together into a risk group classification from 1–5. For patients with higher risk classes (>3), radiotherapy together with hormone therapy is a common treatment option [2].

In radiotherapy (RT), individual treatment plans are created based on the patient’s anatomy. These plans are based on computed tomography (CT), often supplemented with MRI images. MRI and CT complement each other, as MRI has better soft tissue contrast and CT has better bone contrast. Based on the images, the volumes to be treated (target) and the volumes to be avoided (risk organs) are defined. Prostate RT is complex, and there are uncertainties regarding the patient's internal movements and how the patient is positioned before each treatment. To account for these uncertainties, the radiation field is expanded (extended margins to target) to ensure that the treatment volume receives its radiotherapy. RT is most often given in fractions. Fractionation, dose, and treatment volume depend on the patient’s risk category. The treatment area can be, for example, only prostate, prostate with extra radiation dose (boost) to an intraprostatic tumour, or prostate with lymph node (LN) irradiation. LN irradiation is most often given for preventive purposes for PCa with a risk classification >4, which means no cancer has been identified, but any microscopic spread to the LNs is being treated profylactically.

In RT, target identification is essential both in the treatment planning images (CT/MRI) and at treatment. Studies have shown that PCa often re-occurs in or near the volume of the dominant (often largest) intraprostatic tumour [3, 4], and this volume is relevant for boosting. For patients treated with hormone therapy before radiotherapy, tumour identification is complicated. Hormones change the tumour characteristics, affecting the image contrast and making the tumour difficult to identify. To study this, we investigated whether texture analysis could identify the tumour volume after hormone therapy (paper II). However, even with texture analysis, the tumour was difficult to identify. A follow-up study examined whether the image information in MRI images taken before hormone therapy could indicate how the treatment fell out (paper IV). However, no correlation was seen between image features and the progression of PCa.

Identifying the target and correctly positioning the patient for each treatment fraction is the most important procedure in radiotherapy. The prostate is a mobile organ; therefore, intraprostatic fiducial markers are inserted before treatment planning to reduce positioning uncertainties. Each radiotherapy session begins with an X-ray image where the markers are visible, and the radiation can be delivered based on the markers' position.  The markers are also used as guidance for large target volumes, such as for prostate with LN irradiation. With better knowledge of the prostate and LN movements, the margins can potentially be reduced, followed by reduced radiation dose to healthy tissue and therefore reduced side effects for patients. Movements in the radiotherapy volume were the focus of paper I. Using MRI images, the movements of the prostate and LNs were measured during the course of radiotherapy, and we found that LN movement is independent of the movement of the prostate and that the movement varies in the target volume.

In addition to the recurrence of PCa in the tumour area, there is an increased risk of recurrence in the prostate periphery close to the rectum. Since the rectum and prostate are in contact for some patients, RT must be adapted to make rectum side effects tolerable.  One way to increase the distance between the prostate and the rectum is to inject a gel between the two organs. The distance makes it easier to achieve a better dose distribution to the PCa. This idea resulted in paper III, where patients were given a gel between the prostate and rectum. MRI was used to check the stability of the gel during the course of RT and was evaluated together with long-term follow-up of the patient’s well-being and acceptance of the gel. We found that the radiation dose to the rectum was lower with a spacer, although the spacer was not completely stable during treatment.

Place, publisher, year, edition, pages
Umeå: Umeå universitet, 2023. p. 62
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 2225
Keywords
MRI, imaging, prostate, radiotherapy, target detection
National Category
Radiology, Nuclear Medicine and Medical Imaging Cancer and Oncology
Research subject
radiation physics
Identifiers
urn:nbn:se:umu:diva-205285 (URN)978-91-7855-988-6 (ISBN)978-91-7855-989-3 (ISBN)
Public defence
2023-03-30, Hörsal B, Norrlands universitetssjukhus, byggnad 1D, T9, Umeå, 13:00 (English)
Opponent
Supervisors
Funder
Region Västernorrland, 8206
Available from: 2023-03-09 Created: 2023-03-01 Last updated: 2024-07-02Bibliographically approved

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Björeland, UlrikaNotstam, KristinaFransson, PerSöderkvist, KarinBeckman, LarsJonsson, JoakimNyholm, TufveWidmark, AndersThellenberg-Karlsson, Camilla

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