•Overlap volume histograms can be used for prediction models of D2cm3 values.•Prediction models can be used in a multi-center setting to detect suboptimal plans.•Plan quality improvement is possible ...for suboptimal plans detected by the prediction model.
Image-guided adaptive brachytherapy (IGABT) is an important modality in the cervical cancer treatment, and plan quality is sensitive to time pressure in the workflow. Patient anatomy-based quality-assurance (QA) with overlap volume histograms (OVHs) has been demonstrated to detect suboptimal plans (outliers). This analysis quantifies the possible improvement of plans detected as outliers, and investigates its suitability as a clinical QA tool in a multi-center setting.
In previous work OVH-based models were investigated for the use of QA. In this work a total of 160 plans of 68 patients treated in accordance with the current state-of-the-art IGABT protocol from Erasmus MC (EMC) were analyzed, with a model based on 120 plans (60 patients) from UMC Utrecht (UMCU). Machine-learning models were trained to define QA thresholds, and to predict dose D2cm3 to bladder, rectum, sigmoid and small bowel with the help of OVHs of the EMC cohort. Plans out of set thresholds (outliers) were investigated and retrospectively replanned based on predicted D2cm3 values.
Analysis of replanned plans demonstrated a median improvement of 0.62 Gy for all Organs At Risk (OARs) combined and an improvement for 96 % of all replanned plans. Outlier status was resolved for 36 % of the replanned plans. The majority of the plans that could not be replanned were reported having implantation complications or insufficient coverage due to tumor geometry.
OVH-based QA models can detect suboptimal plans, including both unproblematic BT applications and suboptimal planning circumstances in general. OVH-based QA models demonstrate potential for clinical use in terms of performance and user-friendliness, and could be used for knowledge transfer between institutes. Further research is necessary to differentiate between (sub)optimal planning circumstances.
Background The standard of care for locally advanced cervical cancer is concurrent chemoradiation followed by intracavitary brachytherapy (BT). BT forms an integral part of management as it improves ...local control and overall survival. In recent times, image-guided BT (IGBT) has been recommended as the standard of care. Computed tomography (CT) scan-based BT is a cost-effective and easily available modality for IGBT. The aim of the study was to do a dosimetric analysis of CT scan-based BT for patients with cervical cancer. Methods This was a retrospective study and included patients with cervical cancer treated with radical chemoradiation followed by BT. CT scan was done before every fraction after applicator placement, and CT-based planning was done for all fractions. Clinical details were abstracted from the case records, and dosimetric details were collected from the treatment planning systems. Total equivalent dose in 2 Gy per fraction (EQD2) was calculated for external beam radiation therapy and BT target volumes and organs at risk (OARs). Results This study included 50 patients. The mean age was 45 years. The majority of the cases were stage III. The mean high-risk clinical target volume (HRCTV) for the 1st, 2nd, and 3rd fraction was 53.1, 52.1, and 51.3 mL, respectively. Mean D90 HRCTV (dose received by 90% of the HRCTV) dose was 81.4 Gy (EQD2 10 Gy) and D2cc was 75.8 Gy (EQD2 3 Gy) for the rectum and sigmoid and 86.2 Gy (EQD2 3 Gy) for the bladder. Conclusion CT-based BT is a reasonable option in high-volume and low-resource settings where the availability of magnetic resonance imaging is limited. CT-based BT at every fraction can ensure proper applicator placement and aid in optimizing the dose to the target volumes and OARs.
•Overlap volume histograms can be used for prediction models of D2cm3 values.•Prediction models are robust to interstitial needle use and applicator types.•Prediction models can be used in a ...multi-center setting.•Suboptimal plans can be detected when models are trained on high-quality data.
Image-guided adaptive brachytherapy (IGABT) is a key component in the treatment of cervical cancer, but the nature of the clinical workflow makes it vulnerable to suboptimal plans, as the theoretical optimal plan depends heavily on organ configuration. Patient anatomy-based quality-assurance (QA) with overlap volume histograms (OVHs) is a promising tool to detect such suboptimal plans, and in this analysis its suitability as a multi-institutional clinical QA tool is investigated.
A total of 223 plans of 145 patients treated in accordance with the current state-of-the-art IGABT protocols from UMC Utrecht (UMCU) and Erasmus MC (EMC) were included. Machine-learning models were trained to predict dose D2cm3 to bladder, rectum, sigmoid and small bowel with the help of OVHs. For this strategy, points are sampled on the organs-at-risk (OARs), and the distances of the sampled points to the target are computed and combined in a histogram. Machine-learning models can then be trained to predict dose-volume histograms (DVHs) for unseen data. Single-center model robustness to needle use and applicator type and multi-center model translatability were investigated. Performance of models was assessed by the difference between planned (clinical) and predicted D2cm3 values.
Intra-validation of UMCU data demonstrated OVH model robustness to needle use and applicator type. The model trained on UMCU data was found to be robust within the same protocol on EMC data, for all investigated OARs. Mean squared error between planned and predicted D2cm3 values of OARs ranged between 0.13 and 0.40 Gy within the same protocol, indicating model translatability. For the former protocol cohort of Erasmus MC large deviations were found between the planned and predicted D2cm3 values, indicating plan deviation from protocol. Mean squared error for this cohort ranged from 0.84 to 4.71 Gy.
OVH-based models can provide a solid basis for multi-institutional QA when trained on a sufficiently strict protocol. Further research will quantify the model’s impact as a QA tool.
Abstract Background and purpose To analyse dose–response relationships for local control of cervical cancer after MR image-guided brachytherapy (IGBT) based on dose–volume histogram parameters. ...Methods and materials The analysis includes 141 patients with cervix cancer (stages IB–IVA) treated with 45–50.4 Gy EBRT ± cisplatin plus 4 × 7 Gy IGBT. Gross tumour volume (GTV), high risk clinical target volume (HR CTV) and intermediate risk CTV (IR CTV) were delineated and DVH parameters (D90, D100) were assessed. Doses were converted to the equivalent dose in 2 Gy (EQD2) using linear-quadratic model ( α / β = 10 Gy). Groups of patients were formed according to tumour size at diagnosis (GTVD ) of 2–5 cm (group 1) or >5 cm (2), with subgroups of the latter for HR CTV size at first IGBT 2–5 cm (2a) or >5 cm (2b). Dose–response dependence for local recurrence was evaluated by logit analysis. Results Eighteen local recurrences in the true pelvis were observed. Dose–response analyses revealed a significant effect of HR CTV D100 ( p = 0.02) and D90 ( p = 0.005). The ED50-values for tumour control were 33 ± 15 Gy (D100) and 45 ± 19 Gy (D90). ED90-values were 67 Gy (95% confidence interval 50;104) and 86 Gy 77;113, respectively. Conclusions A significant dependence of local control on D100 and D90 for HR CTV was found. Tumour control rates of >90% can be expected at doses >67 Gy and 86 Gy, respectively.
Abstract Purpose To investigate the reproducibility of virtually planned needles, changes in DVH parameters and clinical feasibility of combined intracavitary/interstitial (IC/IS) pulsed dose rate ...brachytherapy (PDR-BT) for locally advanced cervical cancer based on 3D MRI preplanning. Material and methods Fifty-eight consecutively patients accrued in the EMBRACE study were included. Treatment was initiated with external beam radiotherapy and cisplatin. Three BT implants and MRI with the applicator in situ were performed in all patients, i.e. week 5 (BT0), week 6 (BT1) and week 7 (BT2) of the treatment. BT0 was only used for preplanning of subsequent implantations, whereas BT1 and BT2 comprised 2 equal sized fractions of PDR BT. Results Based on BT0, 24 patients (41%) were selected for a combined IC/IS implant at BT1 and BT2. Patients treated with IC/IS BT had significantly larger tumours compared with patients treated with IC BT only ( p < 0.03). Additional time in general anaesthesia for the IC/IS component was on average 16 min. The number of preplanned virtual needles was 5.3 ± 2.7 compared to 5.3 ± 2.9 and 5.4 ± 3.0 needles implanted at BT1 and BT2, respectively ( p = 0.72). Planned needle implantation depth was 33 ± 15 mm compared to 30 ± 10 mm at BT1 and 29 ± 11 mm at BT2 ( p = 0.04). In the 24 patients selected for IC/IS BT both the virtual IC/IS plan (BT0) and the actually delivered plan (BT1 + BT2) significantly increased D90 and D100 for HR CTV ( p < 0.01) and reduced D2cc for sigmoid ( p < 0.01) and bowel ( p = 0.04) compared to the optimised IC preplan (BT0). IC/IS BT was only associated with minor morbidity, which was resolved at a 3-month follow up. Conclusion Combined IC/IS BT based on full 3D MRI preplanning is clinically feasible. The virtual preplanned needle positions are reproducible at subsequent BT applications leading to significantly improved DVH parameters and a clinically feasible and fast implant procedure.
Refinements of brachytherapy techniques have led to better local control of locally advanced cervical cancer (LACC), especially with the development of image-guided adaptive brachytherapy (IGABT). ...Data on the efficacy of brachytherapy in cervical cancer spreading to adjacent organs are scarce. We report the experience of our institution in the treatment of these advanced tumors with IGABT.
Medical records of patients treated for a LACC spreading to the bladder and/or rectum between 2006 and 2020 at Gustave Roussy Institute were analyzed. Dosimetric parameters were collected and converted into 2 Gy per fraction equivalent doses, including the minimal dose received by 90% of the high-risk target volume (D90 CTVHR) and intermediate-risk target volume (D90 CTVIR), as well as the dose received by the most exposed 2 cm3 of the organs at risk. A Cox regression model was used to study the potential associations between clinical and dosimetric factors with survival endpoints and fistula formation.
A total of 81 patients were identified. All patients received pelvic+/− para-aortic radiotherapy, 45 Gy in 25 fractions +/− boost to gross lymph nodes. Concomitant platinum-based chemotherapy was administered in 93.8% of cases. The median D90 CTVHR dose was 75.5 GyEQD2 (SD: 10.39 GyEQD2) and median CTVHR volume was 47.6 cm3 (SD: 27.9 cm3). Median bladder and rectal D2cm3 dose were 75.04 GyEQD2 (SD: 8.72 GyEQD2) and 64.07 GyEQD2 (SD: 6.68 GyEQD2). After a median follow-up of 27.62 ± 25.10 months, recurrence was found in 34/81 patients (42%). Metastatic failure was the most common pattern of relapse (n = 25). Use of a combined interstitial/intracavitary technique and D90 CTVHR ≥ 75.1 GyEQD2 were prognostic factors for OS in univariate analysis (HR = 0.24, 95%IC: 0.057–1, p = 0.023; HR = 0.2, 95%IC: 0.059–0.68, p = 0.0025, respectively). In multivariate analysis, a D90 CTVHR ≥ 75.1 GyEQD2 was significant for OS (HR = 0.23; 95%IC: 0.07, 0.78, p = 0.018). The occurrence of vesicovaginal fistula (VVF) was the most frequent pattern of local recurrence (HR = 4.6, 95%CI: 1.5–14, p = 0.01).
Advances in brachytherapy modalities improved local control and survival while reducing toxicities. Enhancing local control through dose escalation and combined intracavitary/interstitial brachytherapy techniques is a major factor in patients cure probability, together with systemic intensification to better control distant events.
•Dose escalation through combined intracavity/interstitial brachytherapy techniques improves local control in locally advanced cervical cancer•In this study, the following factors were associated with poorer survival without local failure: moderately to poorly differentiated grade, a D90 CTVIR dose <63.5 GyEQD2 and a vesico-vaginal fistula formation•A transverse tumor dimension >55 mm was predictive of fistula during external radiotherapy
•BT compares favorably with EBRT boost inanal cancer chemoradiation.•MRI-guided adaptive BT is expected to improve results further.•Some favorable physical & biological properties of BT cannot be ...matched by EBRT.•Despite this, the use of BT boost remains limited to selected centers.•BT boost for anal cancer should be reevaluated in a prospective clinical study.
Evidence from studies which combined 2D-3D external beam radiotherapy (EBRT) ± chemotherapy with 2D brachytherapy (BT) for anal cancer suggest favorable outcomes when compared with chemo-EBRT alone. Further improvement of results can be expected in the era of intensity modulated EBRT and MRI-guided adaptive BT. Despite this, BT is not discussed as a therapeutic option in the prominent international guidelines and its use remains limited to selected institutions. Special skills, complexity, equipment, cost and reimbursement policies have been highlighted as barriers for its wider implementation. However, these factors are relevant for modern radiotherapy in general. Therefore, it can be argued that the role of BT as a component of chemoradiation should be redefined. We describe the historical evolution and current role of BT boost for anal cancer and outline its potential in the context of combined intensity modulated EBRT, chemotherapy and MRI-guided adaptive BT.
•Local and pelvic control in FIGO1994 stage IB were ≥95% with acceptable morbidity.•We found no isolated local relapse. Pelvic failure occurred in 3%. Most relapses were systemic.•Results of modern ...brachytherapy in early cervical cancer parallel those of modern surgery.
Multiple treatment options are used in early local-stage cervical cancer, including combinations of surgery with neoadjuvant/adjuvant radiotherapy and chemotherapy. Our aim was to determine the outcome for definitive chemoradiation with image guided brachytherapy (IGBT).
FIGO1994 staging system was used in our study. We included 123 patients with stage IB cervical cancer, treated at 12 centers with external beam radiotherapy (EBRT) ± Chemotherapy and IGBT. Three- and 5-year actuarial local control (LC), pelvic control (PC), overall survival (OS), cancer-specific survival (CSS) and late morbidity (CTCAE v 3.0) were computed.
Median age was 48 (23–82) years. FIGO1994 stage distribution was: IB1 68% and IB2 32%; 41% of the entire cohort had nodal metastases and 73% squamous-cell carcinoma. MRI-based tumor size was >40 mm in 63%. Median EBRT dose was 45 (40–50) Gy; 84% received chemotherapy. At IGBT, mean CTV-HR D90 was 93 ± 17 Gy (EQD210). D2cc for bladder was 76 ± 14 Gy, rectum 66 ± 11 Gy, sigmoid 66 ± 10 Gy, bowel 67 ± 7 Gy (EQD23). At 43-months median follow-up, 9% of patients had systemic, 6% paraaortic, 3% pelvic-nodal and 2% local failure. Five-year LC was 98%, PC 96%, CSS 90%, OS 83%. Intestinal G3-–4 morbidity was 8%, urinary 7% and vaginal 0%.
Chemoradiation with IGBT for FIGO1994 stage IB cervical cancer leads to excellent loco-regional control with limited morbidity. In IB node-negative disease, it can be regarded equivalent to surgery in terms of oncologic outcome. In tumors with unfavorable pre-treatment characteristics, chemoradiation is the first choice to avoid combining surgery with adjuvant therapy.
Abstract Background and purpose To compare the dosimetric impact of organ and target variations relative to the applicator for intracavitary brachytherapy by a multicentre analysis with different ...application techniques and fractionation schemes. Material and methods DVH data from 363 image/contour sets (120 patients, 6 institutions) were included for 1–6 fractions per patient, with imaging intervals ranging from several hours to ∼20 days. Variations between images acquired within one (intra-application) or between consecutive applicator insertions (inter-application) were evaluated. Dose plans based on a reference MR or CT image series were superimposed onto subsequent image sets and D 2 cm 3 for the bladder, rectum and sigmoid and D90 for HR CTV were recorded. Results For the whole sample, the systematic dosimetric variations for all organs at risk, i.e. mean variations of D 2 cm 3 , were found to be minor (<5%), while random variations, i.e. standard deviations were found to be high due to large variations in individual cases. The D 2 cm 3 variations (mean ± 1SD) were 0.6 ± 19.5%, 4.1 ± 21.7% and 1.6 ± 26.8%, for the bladder, rectum and sigmoid. For HR CTV, the variations of D 90 were found to be −1.1 ± 13.1% for the whole sample. Grouping of the results by intra- and inter-application variations showed that random uncertainties for bladder and sigmoid were 3–7% larger when re-implanting the applicator for individual fractions. No statistically significant differences between the two groups were detected in dosimetric variations for the HR CTV. Using 20% uncertainty of physical dose for OAR and 10% for HR CTV, the effects on total treatment dose for a 4 fraction HDR schedule at clinically relevant dose levels were found to be 4–8 Gy EQD2 for OAR and 3 Gy EQD2 for HR CTV. Conclusions Substantial variations occur in fractionated cervix cancer BT with higher impact close to clinical threshold levels. The treatment approach has to balance uncertainties for individual cases against the use of repetitive imaging, adaptive planning and dose delivery.
In Japan, the number of patients treated with high-dose-rate brachytherapy is small per facility. The use of radiation equipment in RALS rooms is restricted to the acquisition of images required for ...high-dose-rate brachytherapy, which is a treatment purpose permitted by the current domestic law. The difficulty of installing dedicated CT scanner in RALS rooms has been a stumbling block to the widespread use of IGBTs.Therefore, we conducted a questionnaire survey to determine the effective use of CT in RALS rooms. Because the RALS room CT is used for a limited number of hours and days, there were many requests for its use in CT imaging for treatment planning of external irradiation.We concluded that the availability of RALS room CT, in addition to image acquisition for brachytherapy, will lead to the further spread of IGBTs in Japan.
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