To evaluate prostate intrafraction motion using MRI during the full course of online adaptive MR-Linac radiotherapy (RT) fractions, in preparation of MR-guided extremely hypofractionated RT.
Five low ...and intermediate risk prostate cancer patients were treated with 20 × 3.1 Gy fractions on a 1.5T MR-Linac. Each fraction, initial MRI (Pre) scans were obtained at the start of every treatment session. Pre-treatment planning MRI contours were propagated and adapted to this Pre scan after which plan re-optimization was started in the treatment planning system followed by dose delivery. 3D Cine-MR imaging was started simultaneously with beam-on and acquired over the full beam-on period. Prostate intrafraction motion in this cine-MR was determined with a previously validated soft-tissue contrast based tracking algorithm. In addition, absolute accuracy of the method was determined using a 4D phantom.
Prostate motion was completely automatically determined over the full on-couch period (approx. 45 min) with no identified mis-registrations. The translation 95% confidence intervals are within clinically applied margins of 5 mm, and plan adaption for intrafraction motion was required in only 4 out of 100 fractions.
This is the first study to investigate prostate intrafraction motions during entire MR-guided RT sessions on an MR-Linac. We have shown that high quality 3D cine-MR imaging and prostate tracking during RT is feasible with beam-on. The clinically applied margins of 5 mm have proven to be sufficient for these treatments and may potentially be further reduced using intrafraction plan adaptation guided by cine-MR imaging.
•First delivered dose reconstruction based on six degrees of freedom motion from online 3D cine-MR imaging and treatment log files.•For most fractions no significant target dose decrease ...observed.•Few fractions with outlier motion due to bladder/rectal filling causing large dose deviations.•Automated fast dose reconstruction crucial for future MRI-guided treatments.
Monitoring the intrafraction motion and its impact on the planned dose distribution is of crucial importance in radiotherapy. In this work we quantify the delivered dose for the first prostate patients treated on a combined 1.5T Magnetic Resonance Imaging (MRI) and linear accelerator system in our clinic based on online 3D cine-MR and treatment log files.
A prostate intrafraction motion trace was obtained with a soft-tissue based rigid registration method with six degrees of freedom from 3D cine-MR dynamics with a temporal resolution of 8.5–16.9 s. For each fraction, all dynamics were also registered to the daily MR image used during the online treatment planning, enabling the mapping to this reference point. Moreover, each fraction’s treatment log file was used to extract the timestamped machine parameters during delivery and assign it to the appropriate dynamic volume. These partial plans to dynamic volume combinations were calculated and summed to yield the delivered fraction dose. The planned and delivered dose distributions were compared among all patients for a total of 100 fractions.
The clinical target volume underwent on average a decrease of 2.2% ± 2.9% in terms of D99% coverage while bladder V62Gy was increased by 1.6% ± 2.3% and rectum V62Gy decreased by 0.2% ± 2.2%.
The first MR-linac dose reconstruction results based on prostate tracking from intrafraction 3D cine-MR and treatment log files are presented. Such a pipeline is essential for online adaptation especially as we progress to MRI-guided extremely hypofractionated treatments.
In early-stage breast cancer and DCIS patients, breast-conserving therapy is today’s standard of care. The purpose of this study was to evaluate the relation between the microscopic tumor diameter ...(mTD), the excised specimen (ES) volume, and the irradiated postoperative complex (POC) volume, in patients treated with breast-conserving therapy. In 186 patients with pTis-2N0 breast cancer, the mTDs, ES, and POC volumes (as delineated on the radiotherapy-planning CT scan), were retrospectively determined. Linear regression analysis was performed to study the association between the mTD, and the ES and POC volumes. The explained variance (
r
2
) was calculated to establish the proportion of variation in the outcome variable that could be explained by the determinant (
P
≤ 0.05). Moreover, the influence of tumor characteristics, age, surgical procedures, and breast size was studied. Median mTD was 1.2 cm (range 0.1–3.6 cm), median ES volume was 60 cm
3
(range 6–230 cm
3
) and median POC volume was 15 cm
3
(range 0.5–374 cm
3
). The POC was not clearly visible on the majority of the CT scans, based on a median assigned cavity visualization score of 3 (range 1–5). The explained variance for the mTD on the ES volume was low (
r
2
= 0.08,
P
< 0.001). A slightly stronger association was observed in palpable tumors (
r
2
= 0.23,
P
< 0.001) and invasive lobular carcinomas (
r
2
= 0.39,
P
= 0.01). Furthermore, weak associations were observed between POC volume and mTD (
r
2
= 0.04,
P
= 0.01), and POC and ES volume (
r
2
= 0.23,
P
< 0.001). A weak association was observed between breast volume and ES volume (
r
2
= 0.27,
P
< 0.001). In conclusion, both the excised and the irradiated POC volumes did not show a clinically relevant association with the mTD in women with early-stage breast cancer treated with breast-conserving therapy. Future studies should focus on improvement of surgical localization, development of image-guided, minimally invasive operation techniques, and more accurate image-guided target volume delineation in radiotherapy.
Whole bladder radiotherapy is challenging due to inter- and intrafraction size and shape changes. To account for these changes, currently a Library of Plans (LoP) technique is often applied, but ...daily adaptive radiotherapy is also increasingly becoming available. The aim of this study was to compare LoP with two magnetic resonance imaging guided radiotherapy (MRgRT) strategies by comparing target coverage and volume of healthy tissue inside the planning target volume (PTV) for whole bladder treatments.
Data from 25 MRgRT lymph node oligometastases treatments (125 fractions) were used, with three MRI scans acquired at each fraction at 0, 15 and 30 min. Bladders were delineated and used to evaluate three strategies: 1) LoP with two plans for a 15 min fraction, 2) MRgRT15min for a 15 min fraction and 3) MRgRT30min for a 30 min fraction. The volumes of healthy tissue inside and bladder outside the PTV were analyzed on the simulated post-treatment images.
MRgRT30min had 120% and 121% more healthy tissue inside the PTV than LoP and MRgRT15min. For LoP slightly more target outside the PTV was found than for MRgRT30min and MRgRT15min, with median 0% (range 0–23%) compared to 0% (0–20%) and 0% (0–10%), respectively.
Taking into account both target coverage and volume of healthy tissue inside the PTV, MRgRT15min performed better than LoP and MRgRT30min for whole bladder treatments. A 15 min daily adaptive radiotherapy workflow is needed to potentially benefit from replanning compared to LoP.
•High-grade radiation-induced toxicity was reported in only two patients.•Treatment resulted in improved disease-related symptom management and functioning.•Treatment was, however, also associated ...with worsened impotence.•Other quality of life domains remained stable or stabilized after six to 12 months.•This study supports investigation of dose escalation or boosting with MR-guided RT.
This study assessed quality of life (QoL) and clinical outcomes in rectal cancer patients treated with magnetic resonance (MR) guided short-course radiation therapy (SCRT) on a 1.5 Tesla (T) MR-Linac during the first 12 months after treatment.
Rectal cancer patients treated with 25 Gy SCRT in five fractions with curative intent in the Netherlands (2019–2022) were identified in MOMENTUM (NCT04075305). Toxicity (CTCAE v5) and QoL (EORTC QLQ-C30 and -CR29) was primarily analyzed in patients without metastatic disease (M0) and no other therapies after SCRT. Patients who underwent tumor resection were censored from surgery. A generalized linear mixed-model was used to investigate clinically meaningful (≥10) and significant (P < 0.05) QoL changes. Clinical and pathological complete response (cCR and pCR) rates were calculated in patients in whom response was documented.
A total of 172 patients were included, of whom 112 patients were primarily analyzed. Acute and late radiation-induced high-grade toxicity were reported in one patient, respectively. CCR was observed in 8/64 patients (13 %), 14/37 patients (38 %) and 13/16 patients (91 %) at three, six and twelve months; pCR was observed in 3/69 (4 %) patients. After 12 months, diarrhea (mean difference MD −17.4 95 % confidence interval CI −31.2 to −3.7), blood and mucus in stool (MD −31.1 95 % CI −46.4 to −15.8), and anxiety (MD –22.4 95 % CI −34.0 to −10.9) were improved.
High-field MR-guided SCRT for the treatment of patients with rectal cancer is associated with improved disease-related symptom management and functioning one year after treatment.
Accurate tumor bed delineation after breast-conserving surgery is important. However, consistency among observers on standard postoperative radiotherapy planning CT is low and volumes can be large ...due to seroma formation. A preoperative delineation of the tumor might be more consistent. Therefore, the purpose of this study was to determine the consistency of preoperative target volume delineation on CT and MRI for breast-conserving radiotherapy.
Tumors were delineated on preoperative contrast-enhanced (CE) CT and newly developed 3D CE-MR images, by four breast radiation oncologists. Clinical target volumes (CTVs) were created by addition of a 1.5 cm margin around the tumor, excluding skin and chest wall. Consistency in target volume delineation was expressed by the interobserver variability. Therefore, the conformity index (CI), center of mass distance (dCOM) and volumes were calculated. Tumor characteristics on CT and MRI were scored by an experienced breast radiologist.
Preoperative tumor delineation resulted in a high interobserver agreement with a high median CI for the CTV, for both CT (0.80) and MRI (0.84). The tumor was missed on CT in 2/14 patients (14%). Leaving these 2 patients out of the analysis, CI was higher on MRI compared to CT for the GTV (p<0.001) while not for the CTV (CT (0.82) versus MRI (0.84), p=0.123). The dCOM did not differ between CT and MRI. The median CTV was 48 cm3 (range 28-137 cm3) on CT and 59 cm3 (range 30-153 cm3) on MRI (p<0.001). Tumor shapes and margins were rated as more irregular and spiculated on CE-MRI.
This study showed that preoperative target volume delineation resulted in small target volumes with a high consistency among observers. MRI appeared to be necessary for tumor detection and the visualization of irregularities and spiculations. Regarding the tumor delineation itself, no clinically relevant differences in interobserver variability were observed. These results will be used to study the potential for future MRI-guided and neoadjuvant radiotherapy.
International Clinical Trials Registry Platform NTR3198.
Purpose:
Magnetic resonance imaging (MRI) enables direct characterization of intra‐fraction motion ofbreast tumors, due to high softtissue contrast and geometric accuracy. The purpose is to ...analyzethis motion in early‐stage breast‐cancer patients using pre‐operative supine cine‐MRI.
Methods:
MRI was performed in 12 female early‐stage breast‐cancer patients on a 1.5‐T Ingenia (Philips)wide‐bore scanner in supine radiotherapy (RT) position, prior to breast‐conserving surgery. Twotwodimensional (2D) T2‐weighted balanced fast‐field echo (cine‐MRI) sequences were added tothe RT protocol, oriented through the tumor. They were alternately acquired in the transverse andsagittal planes, every 0.3 s during 1 min. A radiation oncologist delineated gross target volumes(GTVs) on 3D contrast‐enhanced MRI. Clinical target volumes (CTV = GTV + 15 mm isotropic)were generated and transferred onto the fifth time‐slice of the time‐series, to which subsequents lices were registered using a non‐rigid Bspline algorithm; delineations were transformed accordingly. To evaluate intra‐fraction CTV motion, deformation fields between the transformed delineations were derived to acquire the distance ensuring 95% surface coverage during scanning(P95%), for all in‐plane directions: anteriorposterior (AP), left‐right (LR), and caudal‐cranial(CC). Information on LR was derived from transverse scans, CC from sagittal scans, AP fromboth sets.
Results:
Time‐series with registration errors – induced by motion artifacts – were excluded by visual inspection. For our analysis, 11 transverse, and 8 sagittal time‐series were taken into account. Themedian P95% calculated in AP (19 series), CC (8), and LR (11) was 1.8 mm (range: 0.9–4.8), 1.7mm (0.8–3.6), and 1.0 mm (0.6–3.5), respectively.
Conclusion:
Intra‐fraction motion analysis of breast tumors was achieved using cine‐MRI. These first results show that in supine RT position, motion amplitudes are limited. This information can be used for adaptive RT planning, and to develop preoperative partial‐breast RT strategies, such asablative RT for early‐stage breast‐cancer patients.
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.
Detection of grade 3–4 extra mural venous invasion (mrEMVI) on magnetic resonance imaging (MRI) is associated with an increased distant metastases (DM)-rate. This study aimed to determine the impact ...of different grades of mrEMVI and their disappearance after neoadjuvant therapy.
A Dutch national retrospective cross-sectional study was conducted, including patients who underwent resection for rectal cancer in 2016 from 60/69 hospitals performing rectal surgery. Patients with a cT3-4 tumour ≤8 cm from the anorectal junction were selected and their MRI-scans were reassessed by trained abdominal radiologists. Positive mrEMVI grades (3 and 4) were analyzed in regard to 4-year local recurrence (LR), DM, disease-free survival (DFS) and overall survival (OS).
The 1213 included patients had a median follow-up of 48 months (IQR 30–54). Positive mrEMVI was present in 324 patients (27%); 161 had grade 3 and 163 had grade 4. A higher mrEMVI stage (grade 4 vs grade 3 vs no mrEMVI) increased LR-risk (21% vs 18% vs 7%, <0.001) and DM-risk (49% vs 30% vs 21%, p < 0.001) and decreased DFS (42% vs 55% vs 69%, p < 0.001) and OS (62% vs 76% vs 81%, p < 0.001), which remained independently associated in multivariable analysis. When mrEMVI had disappeared on restaging MRI, DM-rate was comparable to initial absence of mrEMVI (both 26%), whereas LR-rate remained high (22% vs 9%, p = 0.006).
The negative oncological impact of mrEMVI on recurrence and survival rates was dependent on grading. Disappearance of mrEMVI on restaging MRI decreased the risk of DM, but not of LR.
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